The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

Provided herein are compositions useful for co-administering with a gene therapy vector to a patient having pre-existing neutralizing antibodies to the viral source of the gene therapy vector capsid. The compositions comprise an FcRn ligand which inhibits specific binding between FcRn and IgG.

Provided herein are compositions useful for co-administering with a gene therapy vector to a patient having pre-existing neutralizing antibodies to the viral source of the gene therapy vector capsid. The compositions comprise an FcRn ligand which inhibits specific binding between FcRn and IgG.

The present invention includes methods for handling live cell compositions in non-nutritive buffer. The cells in the compositions maintain their identity and functional characteristics after being stored in non-nutritive media up to about 72 hours. The storage method enables the cells to be manufactured at a processing facility and shipped to a point of care site. The invention also includes compositions that have been stored in non-nutritive buffer at storage temperatures while maintaining the functional characteristics.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

As disclosed herein, SIRPα is integral to immuno-evasion by many different cancer types as well as cancer resistance to therapies, and reducing SIRPα levels on can bolster antigen acquisition, processing, and presentation, decrease TME immunosuppression and thereby promote tumor-specific T cell activation to eliminate tumors and generate an adaptive immune response consisting of memory T cells, circulating antibodies, and plasma cells, all of which may be specific for neo-antigens in the original cancer. Therefore, disclosed are activated SIRPα.sup.low macrophages that are useful for treating cancers.

Among the various aspects of the present disclosure is the provision of methods and compositions for upregulating MHC class II in cancer cells (e.g., a hematological cancer cell). Also provided are methods of treatment for subjects suffering from hematological cancers, comprising administration of interferon-γ (IFN-γ). The methods of treatment provided herein may be particularly suitable for subjects who have received an allogenic transplant or have suffered a relapse.