Provided herein are methods for manufacturing of tumor reactive T cells that includes ex vivo enrichment of, and expansion of, cells secreting chemokine (C-X-C motif) ligand 13 (CXCL13); cells surface positive for C-X-C chemokine receptor type 5 (CXCR5); and/or one or more of CD39, PD-1 and TIGIT. Also provided are populations of T cells produced by methods described herein and pharmaceutical compositions thereof.
Various embodiments of the invention provide compositions of tumor infiltrating lymphocytes (TILs) enriched in tumor reactive cells. Embodiments also provide methods for manufacturing TILs enriched in tumor reactive cells and uses of the provided enriched tumor reactive TILs for treating cancer in a human or other subject. According to an embodiment, a pharmaceutical T lymphocyte infiltrating (TIL) composition enriched in tumor reactive T cells, comprises an oligoclonal population of tumor infiltrating T cells comprising CD4+ and CD8+ T cells from a tumor, wherein up to 40 clones make up at least 40% of the TCR frequency in the population. Embodiments of the invention are particularly useful for treating tumors that are or have become resistant or refractory to conventional chemotherapy.
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.
Various embodiments of the invention provide recombinant oncolytic viruses engineered to express human cytomegalovirus (HCMV) glycoprotein UL40 and/or Kaposi's sarcoma associated herpesvirus (KSHV) K5 protein, and methods and uses of the same for treating cancer. Also provided are combination therapies involving a T lymphocyte infiltrating (TIL) cell therapy and a provided recombinant oncolytic virus for treating a cancer, including solid tumors.
Various embodiments of the invention provide compositions of tumor infiltrating lymphocytes (TILs) enriched in tumor reactive cells, methods for manufacturing TILs enriched in tumor reactive cells and methods and uses of the provided enriched tumor reactive TILs for treating cancer in a human or other subject. Among the provided embodiments of TIL compositions may include those that exhibit substantial tumor reactivity activity, including degranulation and the ability to express one or more of IFN-gamma and TNF-alpha, in response to antigen presenting cells presenting neo antigenic peptides.
Provided herein are methods for ex vivo expansion of a T cells, including tumor-reactive T cells, and compositions containing such T cells. Also provided are methods for treating diseases and conditions such as cancer using compositions of the present disclosure.
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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
8.
METHODS FOR INDUCING AN IMMUNE RESPONSE AGAINST NEOANTIGENS
Provided herein is a method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a priming composition comprising a peptide antigen conjugate and at least a first boost. The first boost comprises a first oncolytic virus comprising a genome that expresses a first peptide or a second peptide, wherein the first and second peptide are each capable of inducing an immune response to at least one neoantigen. The method further comprises administering the subject a second boost, comprising a second oncolytic virus comprising a genome that expresses a third peptide or a fourth peptide, wherein the third peptide and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen.
Provided herein are methods for ex vivo expansion of a T cells including tumor-reactive T cells, and compositions containing such T cells. Also provided are methods for treating diseases and conditions such as cancer using compositions of the present disclosure.
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell linesTissuesCultivation or maintenance thereofCulture media therefor
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
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
Provided herein are methods for manufacturing T cells. In certain embodiments, methods for manufacturing T cells which express a novel group of cell surface receptors that recognize peptides on the surface of a target cell are provided. Also provided herein are populations of T cells produced by methods described herein and pharmaceutical compositions thereof.
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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
Provided herein is a method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a priming composition comprising a peptide antigen conjugate and at least a first boost. The first boost comprises a first oncolytic virus comprising a genome that expresses a first peptide or a second peptide, wherein the first and second peptide are each capable of inducing an immune response to at least one neoantigen. The method further comprises administering the subject a second boost, comprising a second oncolytic virus comprising a genome that expresses a third peptide or a fourth peptide, wherein the third peptide and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen.
Provided herein is a method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a priming composition comprising a peptide antigen conjugate and at least a first boost. The first boost comprises a first oncolytic virus comprising a genome that expresses a first peptide or a second peptide, wherein the first and second peptide are each capable of inducing an immune response to at least one neoantigen. The method further comprises administering the subject a second boost, comprising a second oncolytic virus comprising a genome that expresses a third peptide or a fourth peptide, wherein the third peptide and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen.
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences, amenability for large scale manufacturing, and safety.
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 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
The disclosure relates to modified orthopoxvirus vectors, as well as methods of using the same for the treatment of various cancers. The disclosure provides modified orthopoxvirus vectors that exhibit various beneficial therapeutic activities, including enhanced oncolytic activity, spread of infection, immune evasion, tumor persistence, capacity for incorporation of exogenous DNA sequences and safety. The viruses we have discovered are also amenable to large scale manufacturing protocols.
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