Provided herein are recombinant fusion polypeptides comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. For example, provided herein are recombinant fusion polypeptides comprising two or more antigenic peptides (e.g., fused to a PEST-containing peptide), wherein each antigenic peptide comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides are fragments of the same cancer-associated protein. Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria or Listeria strains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
This disclosure provides compositions, including Listeria delivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.
Listeria delivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.
Methods and compositions are provided for assessing antigen presentation and potency of Listeria-based immunotherapeutics in inducing an immune response.
Provided herein are tumor-associated antigen peptides comprising heteroclitic mutations and fusion polypeptides comprising such heteroclitic peptide. Also provided are nucleic acids encoding such peptides and fusion polypeptides, recombinant bacteria or Listeria strains comprising such peptides, fusion polypeptides, or nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such peptides, fusion polypeptides, nucleic acids, and recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such peptides, fusion polypeptides, nucleic acids, or recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such peptides, recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
7.
Compositions and methods for lyophilization of bacteria or listeria strains
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Methods and compositions are provided for lyophilization of bacteria or Listeria strains, such as Listeria monocytogenes. Provided are methods for producing a lyophilized composition comprising a bacteria or Listeria strain, formulations for lyophilization comprising a bacteria or Listeria strain, lyophilized bacteria or Listeria strains, and methods of preparing frozen bacteria or Listeria strains for lyophilization.
Listeria delivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
Provided herein are vaccines comprising one or more disease-associated antigenic peptides or nucleic acids encoding one or more disease-associated antigenic peptides and immunogenic compositions comprising such vaccines in combination with an inhibitor of SERPINA1, CRP, TIMP-1, or VEGF. Also provided are methods and compositions for combination therapy between immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains and an inhibitor of SERPINA1, CRP, TIMP-1, orVEGF. Also provided are methods of inducing an immune response against a disease, method of inducing an enhanced immune response against a disease, and method of increasing the overall survival rate of a subject having a disease using such vaccines and immunogenic compositions.
Provided herein are recombinant fusion polypeptides comprising an HPV16 antigenic peptide and an HPV18 antigenic peptide, wherein the HPV16 antigenic peptide and the HPV18 antigenic peptide are operably linked in tandem (e.g., fused to a PEST- containing peptide). Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria or Listeria strains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.
Provided herein are recombinant fusion polypeptides comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. For example, provided herein are recombinant fusion polypeptides comprising two or more antigenic peptides (e.g., fused to a PEST-containing peptide), wherein each antigenic peptide comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides are fragments of the same cancer-associated protein. Also provided are nucleic acids encoding such fusion polypeptides, recombinant bacteria or Listeria strains comprising such fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such recombinant fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Provided herein are systems comprising recurrent cancer mutation immunotherapy compositions and personalized neoepitope immunotherapy compositions. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising a nucleic acid comprising an open reading frame encoding a recombinant fusion polypeptide comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to two or more antigenic peptides, wherein each of the antigenic peptides comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides comprise different recurrent cancer mutations and are fragments of the same cancer-associated protein. Also provided are personalized immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to one or more antigenic peptides, wherein each of the antigenic peptides comprises a cancer-specific neoepitope comprising a cancer-specific mutation found in a cancer sample from a subject but not in a healthy biological sample from the subject. Also provided are recombinant fusion polypeptides, nucleic acids encoding fusion polypeptides, and methods of generating such compositions. Also provided are methods of inducing an anti-tumor-associated-antigen immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such immunotherapy compositions, recombinant fusion polypeptides, nucleic acids, or recombinant bacteria or Listeria strains.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
23.
COMBINATION OF LISTERIA-BASED VACCINE WITH ANTI-CTLA-4 OR ANTI-CD137 ANTIBODIES
The subject matter described herein is directed to methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated tumor or cancer, comprising the step of administering to a subject a recombinant Listeria strain expressing a construct comprising at least one human papillomavirus antigen in combination with one or more other therapeutic agents to treat a tumor or metastatic cancer.
A61K 39/39 - Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
A61K 39/00 - Medicinal preparations containing antigens or antibodies
24.
LISTERIA-BASED IMMUNOGENIC COMPOSITIONS COMPRISING WILMS TUMOR PROTEIN ANTIGENS AND METHODS OF USE THEREOF
Provided are Listeria-based immunogenic compositions comprising Wilms tumor protein (WT1) antigens and methods for treating and vaccinating against cancer and inducing an immune response against the same in a subject. Also provided herein are recombinant fusion polypeptides or chimeric polypeptides comprising Wilms tumor protein antigens, nucleic acids encoding such chimeric polypeptides or fusion polypeptides, recombinant bacteria or Listeria strains comprising such chimeric polypeptides or fusion polypeptides or such nucleic acids, and cell banks comprising such recombinant bacteria or Listeria strains. Also provided herein are methods of generating such chimeric polypeptides or fusion polypeptides, such nucleic acids, and such recombinant bacteria or Listeria strains. Also provided are immunogenic compositions, pharmaceutical compositions, and vaccines comprising such chimeric polypeptides or fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains. Also provided are methods of inducing an anti-WT1 immune response in a subject, methods of inducing an anti-WT1-expressing-tumor or anti-WT1-expressing-cancer immune response in a subject, methods of treating a WT1-expressing or WT1-associated tumor or cancer in a subject, methods of preventing a WT1-expressing or WT1-associated tumor or cancer in a subject, and methods of protecting a subject against a WT1-expressing or WT1-associated tumor or cancer using such recombinant chimeric polypeptides or fusion polypeptides, nucleic acids, recombinant bacteria or Listeria strains, immunogenic compositions, pharmaceutical compositions, or vaccines.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
25.
PERSONALIZED DELIVERY VECTOR-BASED IMMUNOTHERAPY AND USES THEREOF
Disclosed herein is a personalized immunotherapy composition for a subject having a disease or condition, including therapeutic vaccine delivery vectors and methods of making the same comprising gene expression constructs expressing frameshift-mutation-derived peptides associated with one or more neo-epitopes encoded by nucleic acid sequences comprising at least one frameshift mutation, wherein the frameshift mutation is specific to a subject's cancer or unhealthy tissue. A delivery vector of this disclosure includes bacterial vectors; or viral vectors, or peptide vaccine vectors; or DNA vaccine vectors including Listeria bacterial vectors comprising one or more fusion proteins comprising one or more frameshift-mutation-derived peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. Disclosed are also methods of using these compositions for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection in the subject.
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
26.
LISTERIA-BASED IMMUNOTHERAPY AND METHODS OF USE THEREOF
The disclosure relates to the combined use of an immunotherapeutic composition comprising recombinant Listeria strains expressing a heterologous antigen fused to a truncated listeriolysin O (tLLO), a truncated ActA protein, or a PEST amino acid sequence and an antibiotic regimen, which may be sequentially administered in order to prevent the persistence, seeding of Listeria and/or formation of Listeria biofilms while allowing for an anti-tumor/ anti-cancer or anti infectious disease immunotherapeutic response to take place. Disclosed are also methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering the above composition.
A61K 31/7036 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
27.
MANUFACTURING DEVICE AND METHOD OF AN IMMUNOTHERAPEUTIC FORMULATION COMPRISING A RECOMBINANT LISTERIA STRAIN
Provided herein are an apparatus and process for manufacturing a formulation comprising a drug substance, said drug substance comprising a recombinant Listeria strain comprising a prostate specific antigen (PSA) or a chimeric HER2 antigen fused to a Listeriolysin O (LLO) protein fragment.
C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
A61K 38/16 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
29.
RECOMBINANT LISTERIA VACCINE STRAINS AND METHODS OF USING THE SAME IN CANCER IMMUNOTHERAPY
The present invention provides methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated tumor or cancer, comprising the step of administering to a subject a recombinant Listeria strain expressing a construct comprising at least one human papillomavirus antigen.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
Inventor
Wallecha, Anu
Paterson, Yvonne
Abstract
The present invention discloses a process for manufacturing a formulation comprising a drug substance, said drug substance comprising a recombinant Listeria comprising a human papilloma virus (HPV) antigen fused to a Listeriolysin O (LLO) protein fragment. The invention further discloses methods of using treating, protecting against, and inducing an immune response against cervical cancer comprising administration of the recombinant Listeria strain. The present invention also provides methods for inducing an anti-E7 CTL response in a human subject and treating HPV-mediated diseases, disorders, and symptoms, comprising administration of the recombinant Listeria strain.
Disclosed herein are recombinant Listeria strains comprising nucleotides encoding two or more heterologous antigens each fused to a truncated LLO, an N-terminal ActA or a PEST-sequence, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present invention provides methods of treating cervical cancers, comprising the step of administering to a subject a composition comprising a recombinant Listeria expressing an human papilloma virus antigen. In another embodiment, the present invention provides a method of treating cervical cancers, comprising the step of administering a combination therapy comprising a chemo-radiation therapy and a recombinant Listeria strain expressing a human papilloma virus antigen.
Listeria strain comprising a recombinant nucleic add, said nucleic add comprising a first open reading frame encoding a recombinant polypeptide comprising a first N-terminal fragment of an LLO protein fused to a heterologous antigen or fragment thereof, and wherein said recombinant nucleic add further comprises a second open reading frame encoding a mutant PrfA protein.
This invention provides a system of providing and a process of creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic vaccine delivery vectors comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to an subject's cancer or unhealthy tissue. The invention further provides a scalable fully enclosed single use cell growth system, wherein the entire process of manufacturing of personalized immunotherapeutic compositions, up to and including dispensing said composition into containers for patient delivery is carried out within a single enclosed fluid flow path.
This invention provides a system of providing and creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic immunotherapy delivery vectors and methods of making the same comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to a subject's cancer or unhealthy tissue. A delivery vector of this invention includes bacterial vectors including Listeria bacterial vectors; or viral vectors, peptide immunotherapy vectors; or DNA immunotherapy vectors, comprising one or more fusion proteins comprising one or more peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. This invention also provides methods of using the same for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection, or an autoimmune disease or an organ transplant rejection in the subject.
The present invention relates to compositions comprising a recombinant attenuated Listeria strain expressing a truncated ActA and fusion proteins thereof and methods of using the same for inducing anti-disease immune responses, and treatment of the same, including a tumor growth or cancer. In particular, the invention relates to the treatment of a tumor growth or cancer using a live attenuated recombinant Listeria strain that expresses a fusion protein of a truncated ActA fused to an antigen.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
ADVAXIS, INC. (USA)
Inventor
Beatty, Gregory L.
Knoblock, Dawson
Petit, Robert
Princiotta, Michael F.
Wallecha, Anu
Abstract
The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to the treatment of pancreatic cancer using an antagonist of a Programmed Death 1 protein (PD-1) in combination with a live attenuated recombinant Listeria strain comprising a fusion protein of a PEST sequence-containing polypeptide fused to a tumor-associated antigen.
This disclosure provides compositions, including Listeria delivery vectors comprising minigene expression constructs, and methods of using the same for inducing an immune response against an antigen-expressing tumor and for treating the same, and vaccinating against the same in subjects bearing the tumors.
This disclosure provides methods and compositions for using Listeria monocytogenes as an adjuvant for enhancing immune responses in a subject. In certain instances, methods of this disclosure may be useful for subjects receiving a transplant.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
ADVAXIS, INC. (USA)
Inventor
Petit, Robert
Wallecha, Anu
Paterson, Yvonne
Singh, Reshma
Abstract
The disclosure is directed to compositions comprising an oncolytic virus, chimeric antigen receptor T cells (CAR T cells), a therapeutic or immunomodulating monoclonal antibody, a targeting thymidine kinase inhibitor (TKI), or an adoptively transferred cells incorporating engineered T cell receptors, and a live attenuated recombinant Listeria strain comprising a fusion protein of a Truncated LLO, a truncated ActA or a PEST-sequence peptide fused to a tumor-associated antigen. The disclosure is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering the same, with or without an additional radiation therapy treatment.
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C12N 15/62 - DNA sequences coding for fusion proteins
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 14/025 - Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
Disclosed herein are compositions comprising use of compositions comprising a live attenuated recombinant Listeria strain comprising a fusion protein of a truncated listeriolysin O (LLO) protein, a truncated ActA protein, or a PEST amino acid sequence fused to a heterologous antigen, including a tumor-associated antigen, wherein the compositions further comprise or are co-administered with an antibody or fragment thereof. Also disclosed are combination therapies comprising use of these compositions comprising live attenuated recombiant Listeria strains, in conjuction with an antibody or fragment thereof for use in treating, protecting against, and/or inducing an immune response against a tumor, especially wherein the treating, protection against and/or inducing an immune response increases percent survival in a subject.
C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
C12N 15/31 - Genes encoding microbial proteins, e.g. enterotoxins
C07K 14/025 - Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
C07K 14/195 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed herein are recombinant Listeria strains comprising nucleotides encoding two or more heterologous antigens each fused to a truncated LLO, an N-terminal ActA or a PESTsequence, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Listeria based strain that expresses prostate-tissue specific antigen (PSA), and the use of the combination therapies for the treatment of prostate cancer.
THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (USA)
Inventor
Petit, Robert
Wallecha, Anu
Khleif, Samir
Chen, Zhisong
Berzofsky, Jay A.
Abstract
The present invention is directed to compositions comprising an immune checkpoint inhibitor or a T cell stimulator or a combination thereof, and a live attenuated recombinant Listeria strain comprising a fusion polypeptide comprising a truncated Listeriolysin O protein, a truncated ActA protein, or a PEST amino acid sequence fused to a tumor-associated antigen. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor or a cancer, comprising the step of administering the same.
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Listeria based strain that expresses prostate-tissue specific antigen (PSA), and the use of the combination therapies for the treatment of prostate cancer.
Disclosed herein are recombinant nucleic acids encoding tumor antigens fused to immunogenic polypeptides and recombinant Listeria strains comprising the same, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
The present invention provides methods of treating, protecting against and inducing an immune response against a tumor or cancer, comprising the step of administering to a subject a recombinant Listeria strain. In one embodiment the present invention relates to a recombinant Listeria strain, said recombinant Listeria strain comprising a recombinant nucleic add, said nucleic add comprising a first open reading frame encoding a recombinant polypeptide comprising a first N-terminal fragment of an LLO protein fused to a heterologous antigen or fragment thereof, and wherein said recombinant nucleic add further comprises a second open reading frame encoding a mutant PrfA protein.
NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT NIH DIVISION OF EXTRAMURAL INVENTIONS AND TECHNOLOGY RESOURCES (DEITR) (USA)
Inventor
Petit, Robert
Wallecha, Anu
Chen, Zhisong
Berzofsky, Jay A.
Khleif, Samir
Abstract
The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and tumor-associated antigen.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
ADVAXIS, INC. (USA)
Inventor
Shahabi, Vafa
Wallecha, Anu
Maciag, Paulo C.
Paterson, Yvonne
Mason, Nicola
Seavey, Matthew
Abstract
This invention provides compositions and methods for treating and vaccinating against a HER2/neu antigen-expressing tumor and inducing an immune response against the same in a subject.
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
Inventor
Shahabi, Vafa
Wallecha, Anu
Maciag, Paulo C.
Paterson, Yvonne
Mason, Nicola
Seavey, Matthew
Abstract
This invention provides compositions and methods for treating and vaccinating against a HER2/neu antigen-expressing tumor and inducing an immune response against the same in a subject.
This invention provides methods and compositions for using evaluating biomarker expression in a disease and providing a multi-targeted Listeria-based immunotherapeutic approach against said disease. In a related aspect, the invention relates to a method of treating a disease in a subject, the method comprising the steps of: a. obtaining a biological sample from said subject; b. evaluating the expression of a predetermined number of biomarkers in said biological sample; c. administering to said subject a composition comprising a recombinant Listeria strain, said strain comprising a nucleic acid sequence encoding at least one fusion protein, wherein said fusion protein comprises a biomarker identified in said biological sample, wherein said biomarker is associated with said disease, wherein said biomarker is fused to a PEST-containing polypeptide, and wherein each fusion protein within said Listeria comprises a ' different biomarker, thereby treating said disease in said subject.
Listeria genome in an open reading frame with a nucleic acid sequence encoding a PEST-containing polypeptide, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Listeria genome in an open reading frame with a nucleic acid sequence encoding a PEST-containing polypeptide, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
C12N 15/74 - Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
A61K 39/00 - Medicinal preparations containing antigens or antibodies
This invention provides methods and compositions for using a live attenuated Listeria for inhibiting cell-mediated suppression of anti-disease infiltrating T lymphocytes in a subject having the disease.
This invention provides compositions and methods for treating and vaccinating and inducing an immune response against a Her2/neu antigen-expressing tumor in a non-human animal. An exemplary method of treating a Her-2/neu-expressing tumor growth or cancer in a non-human animal, the method comprising the step of administering a recombinant Listeria comprising nucleic acid molecule encoding a fusion polypeptide, wherein said fusion polypeptide comprises a Her2/neu chimeric antigen fused to an additional adjuvant polypeptide is provided.
The Trustees of the University of Pennsylvania (USA)
Inventor
Shahabi, Vafa
Wallecha, Anu
Maciag, Paulo C.
Paterson, Yvonne
Mason, Nicola
Seavey, Matthew
Abstract
This invention provides compositions and methods for treating and vaccinating against an Her2/neu antigen-expressing tumor and inducing an immune response against dominant in a non-human animal.
The Trustees Of The University Of Pennsylvania (USA)
Inventor
Shahabi, Vafa
Wallecha, Anu
Maciag, Paulo C.
Paterson, Yvonne
Seavey, Matthew
Abstract
This invention provides compositions and methods for treating and vaccinating against an Her2/neu antigen-expressing tumor and inducing an immune response against dominant and several sub-dominant epitopes of the antigen.
This invention provides compositions and methods for treating and vaccinating against an Her2/neu antigen-expressing tumor and inducing an immune response against dominant and several sub-dominant epitopes of the antigen.
Provided herein are recombinant Listeria strains expressing a tumor-specific antigenic polypeptide and, optionally, an angiogenic polypeptide wherein a nucleic acid molecule encoding at least one of the polypeptides is operably integrated into the Listeria genome in an open reading frame with a nucleic acid sequence encoding a PEST-containing polypeptide, methods of preparing same, and methods of inducing an immune response, and treating, inhibiting, or suppressing cancer or tumors comprising administering same.
The present invention provides a recombinant Listeria strain, comprising a first peptide fused to an Human Papilloma Virus (HPV) E7 antigen, wherein said first peptide is selected from (a) an N-terminal fragment of an LLO protein; (b) an ActA protein or N-terminal fragment thereof; and (c) a PEST-like sequence-containing peptide for uses related to treating and protecting against cervical cancer. The present invention also provides use of the recombinant Listeria strain in methods for inducing an anti-E7 CTL response in a human subject and for treating HPV-mediated diseases, disorders, and symptoms.
A61K 39/295 - Polyvalent viral antigensMixtures of viral and bacterial antigens
C12N 15/79 - Vectors or expression systems specially adapted for eukaryotic hosts
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
67.
Compositions and methods comprising KLK3 of FOLH1 antigen
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA (USA)
ADVAXIS (USA)
Inventor
Rothman, John
Paterson, Yvonne
Verch, Thorsten
Weiss, Amanda
Bassett, Philip
Abstract
The present invention provides methods for cryopreservation and lyophilization of a Listeria strain, methods for producing a cell bank or a batch of vaccine doses of same, methods of characterizing same, and defined microbiological media.
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