Abstract: Disclosed are novel adoptive cell therapies comprising engineered CD4+ T cells comprising novel T cell receptors and methods of their use in the treatment of cancer. Further, wherein an engineered CD4+ T cell comprising a T cell receptor (TCR) alpha (TCRa) chain comprising a complimentary determining region (CDR) 3 (CDR3) is disclosed.

Abstract: Disclosed herein is a method of providing an anti-cancer immunity in a subject with a bone metastatic cancer. The method involves co-administering to the subject an effective amount of a gamma-delta T cell stimulating agent and an effective amount of a ?? CAR T cell that binds a tumor antigen. Also disclosed herein is a recombinant T cell that expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) polypeptide.

Abstract: In one aspect, disclosed herein are novel multimeric costimulatory agonistic constructs comprising said monomers for expanding tumor infiltrating lymphocytes (TILs) in vitro or ex vivo said methods comprising obtaining TILs and culturing the TILs in media comprising one or more multimeric costimulatory agonists.

Abstract: Disclosed herein is a method for enhancing adoptively transferred autologous or allogeneic immune effector T-cells (including gamma delta T cells (??-T cells)) by targeting the thioredoxin (TRX)-interacting protein (TXNIP). In addition, disclosed herein are cDNA sequences for the co-expression of immune receptors (CARs, TCRs, etc) in combination with guide RNAs, and/or artificial or natural microRNAs, and/or shRNAs targeting TXNIP.

Abstract: Compositions and methods are disclosed for targeted treatment of lung cancer-derived metastatic brain tumors. In particular, tumor targeting agents comprising targeting peptides are disclosed that can target a payload, such as a therapeutic or diagnostic agent, to lung cancer-derived metastatic brain tumors. Chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill lung cancer-derived metastatic brain tumors.

Abstract: Sotorasib augments the KRAS-G12C mutant cancer cells response to TNF? by Increasing TNFR1 surface expression, which in turn upregulates TNF? and IFNy down-stream target genes and ultimately enhances cancer cell death. In TACE-dependent mechanism, Sotorasib inhibited TNFR1 shedding off the KRAS-G12C mutant cancer cells. Additionally, Sotorasib significantly promotes the expansion of tumor infiltrating lymphocytes (TILs). In, addition, it generates a “hot” tumor microenvironment with strikingly augmented T cell effector phenotype. These results suggest that sotorasib regulation of TNFa and IFNy plays a crucial role in generating a more immune active tumor microenvironment. Consistently, sotorasib combined with CAR-T adoptive cell transfer and anti-PD1 treatment enhanced their anti-tumor effect.

Abstract: Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are genetically engineered to express chimeric antigen receptor (CAR) polypeptides to produce CAR-TILs that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed CAR-TILs.

Abstract: Disclosed herein is a method of providing an anti-cancer immunity in a subject with a bone metastatic cancer. The method involves co-administering to the subject an effective amount of a gamma-delta T cell stimulating agent and an effective amount of a ?? CAR T cell that binds a tumor antigen, such as a prostate antigen for bone metastatic prostate cancer, or a breast cancer antigen for bone metastatic breast cancer. Also disclosed herein is a recombinant T cell that expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) polypeptide.

Abstract: Disclosed herein is a method for predicting the responsiveness of a subject to CD40 agonist therapy, such as agonist anti-CD40 therapy, that involves assaying a tumor sample from the subject for a 12 Chemokine gene signature demonstrating that the tumor comprises tertiary lymphoid structures containing B cells. Therefore, also disclosed herein is a method of treating tumors, such as solid tumors, in a subject that involves administering to the subject an effective amount of a composition comprising assaying a tumor sample from the subject for a 12 Chemokine gene signature demonstrating that the tumor comprises tertiary lymphoid structures (TLS) containing B cells, and treating the subject with CD40 agonist therapy, such an agonist anti-CD40 antibody.

Abstract: Compositions and methods are disclosed for targeted treatment of lung cancer-derived metastatic brain tumors. In particular, tumor targeting agents comprising targeting peptides are disclosed that can target a payload, such as a therapeutic or diagnostic agent, to lung cancer-derived metastatic brain tumors. Chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill lung cancer-derived metastatic brain tumors.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill IL13Ra2-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with an IL13Ra2-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides, which can be used with adoptive cell transfer to target and kill cancers, that comprise a costimulatory signaling region having a mutated form of a cytoplasmic domain of CD28 with altered phosphorylation at Y206 and/or Y218. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an antitumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed herein is a method for enhancing adoptively transferred autologous or allogeneic immune effector cells (T cells) in patients who are HLA-C1+. In some embodiments, the method involves ablating KIR2DL2 expression in the T cells prior to adoptive transfer. In some embodiments, the T cells are further engineered to express a CAR. Therefore, disclosed herein are enhanced CAR-T cells that are engineered to have ablated KIR2DL2 expression or activity.

Abstract: Disclosed are compositions and methods for targeted treatment of SSTR-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill SSTR-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a SSTR-expressing cancer, such as a neuroendocrine tumor, that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Compositions and methods are disclosed for targeted treatment of lung cancer-derived metastatic brain tumors. In particular, tumor targeting agents comprising targeting peptides are disclosed that can target a payload, such as a therapeutic or diagnostic agent, to lung cancer-derived metastatic brain tumors. Chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill lung cancer-derived metastatic brain tumors.

Abstract: Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill cancer cells that express TLR9 on their surface. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a TLR9-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Abstract: Disclosed herein is a method of providing an anti-cancer immunity in a subject with a bone metastatic cancer. The method involves co-administering to the subject an effective amount of a gamma-delta T cell stimulating agent and an effective amount of a ?? CAR T cell that binds a tumor antigen, such as a prostate antigen for bone metastatic prostate cancer, or a breast cancer antigen for bone metastatic breast cancer. Also disclosed herein is a recombinant T cell that expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) polypeptide.