Abstract: Methods for treating liver immune dysfunction in a subject are provided. The liver immune dysfunction may be induced by at least one tumor resulting from metastasis in the liver or at least one primary liver cancer. An exemplary method comprises administering to the subject a toll-like receptor 9 (TLR9) agonist, for example, a TLR 9 agonist having the structure: 5?-TCG AAC GTT CGA ACG TTC GAA CGT TCG AAT-3. The TLR9 agonist is administered to the liver, for example, the TLR9 agonist may be administered to the liver using a locoregional therapy through the vasculature.

Abstract: Embodiments of the present invention provide for methods of treating cancer and methods of delivering checkpoint inhibitors to solid tumors in the liver using a locoregional therapy through the vasculature. In one aspect, the present invention relates to a method of treating metastases of colorectal cancer of the liver comprising administering of checkpoint inhibitors to the liver. In another aspect, the present invention relates to a method of treating pancreatic cancer comprising administering checkpoint inhibitors to the pancreas.

Abstract: Embodiments of the present invention provide for methods of treating cancer and methods of delivering toll-like receptor (TLR) agonists to solid tumors in the liver using a locoregional therapy through the vasculature. In one aspect, the present invention relates to a method of treating primary liver cancers such as hepatocellular carcinoma (HCC) and intra-hepatic cholangiocarcinoma (ICC) comprising administering TLR9 agonists to the liver.

Abstract: Embodiments of the present invention provide for methods of treating cancer and methods of delivering toll-like receptor (TLR) agonists to solid tumors in the pancreas using a locoregional therapy through the vasculature. In one aspect, the present invention relates to a method of treating pancreatic cancer comprising administering TLR agonists to the pancreas.

Abstract: Embodiments of the present invention provide for methods of treating cancer and methods of delivering toll-like receptor (TLR) agonists to solid tumors in the liver using a locoregional therapy through the vasculature. In one aspect, the present invention relates to a method of treating metastases of uveal melanoma of the liver comprising administering TLR9 agonists to the liver.

Abstract: Chimeric antigen receptors (CARs) expressing T cells are a promising form of immunotherapy for solid tumors. CAR-T cells from geriatric donors (gCART) are shown herein to be functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared to gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of pERK, pAKT, pSTAT3 and pSTAT5. Furthermore, yCAR-T contained higher proportions of CD4 and CD8 effector memory cells (EM) which are known to have enhanced cytolytic capabilities. In accordance with higher numbers of CD4 and CD8 EM, yCAR-T demonstrated higher levels of CEA specific cytotoxicity compared to gCAR-T, with maximum cytotoxicity observed in IL15 treated yCAR-T cells.

Abstract: Disclosed herein are compositions and methods for the treatment of liver metastases in a subject. The methods include hepatic arterial infusion (HAI) of chimeric antigen receptor modified T cells (CAR-T) which are highly specific for tumor antigens such as carcinoembryonic antigen (CEA). The HAI method is optimized to maximize exposure of the modified cells to the metastatic cells while minimizing exposure to healthy cells. The methods include co-administration of a second therapeutic agent, such as IL-2.

Abstract: Disclosed herein are compositions and methods for the treatment of liver metastases in a subject. The methods include hepatic arterial infusion (HAI) of chimeric antigen receptor modified T cells (CAR-T) which are highly specific for tumor antigens such as carcinoembryonic antigen (CEA). The HAI method is optimized to maximize exposure of the modified cells to the metastatic cells while minimizing exposure to healthy cells. The methods include co-administration of a second therapeutic agent, such as IL-2.

Abstract: The present disclosure provides compositions and methods for treating a peritoneal cancer in a subject. The methods include administering a T cell which is genetically modified to express a chimeric T cell receptor protein. The chimeric T cell receptor protein may include a T cell receptor signaling domain fused to the tumor associated antigen-binding fragment of an antibody or a T cell receptor signaling domain fused to a naturally occurring ligand which specifically binds to a tumor cell surface protein. The compositions and methods disclosed herein are therapeutically effective to reduce, for example, tumor burden, abdominal ascites, peritoneal mucin, or serum tumor marker levels.

Abstract: The present disclosure provides compositions and methods for treating a peritoneal cancer in a subject. The methods include administering a T cell which is genetically modified to express a chimeric T cell receptor protein. The chimeric T cell receptor protein may include a T cell receptor signaling domain fused to the tumor associated antigen-binding fragment of an antibody or a T cell receptor signaling domain fused to a naturally occurring ligand which specifically binds to a tumor cell surface protein. The compositions and methods disclosed herein are therapeutically effective to reduce, for example, tumor burden, abdominal ascites, peritoneal mucin, or serum tumor marker levels.

Abstract: The present disclosure provides compositions and methods for treating a peritoneal cancer in a subject. The methods include administering a T cell which is genetically modified to express a chimeric T cell receptor protein. The chimeric T cell receptor protein may include a T cell receptor signaling domain fused to the tumor associated antigen-binding fragment of an antibody or a T cell receptor signaling domain fused to a naturally occurring ligand which specifically binds to a tumor cell surface protein. The compositions and methods disclosed herein are therapeutically effective to reduce, for example, tumor burden, abdominal ascites, peritoneal mucin, or serum tumor marker levels.

Abstract: Disclosed herein are compositions and methods for the treatment of liver metastases in a subject. The methods include hepatic arterial infusion (HAI) of chimeric antigen receptor modified T cells (CAR-T) which are highly specific for tumor antigens such as carcinoembryonic antigen (CEA). The HAI method is optimized to maximize exposure of the modified cells to the metastatic cells while minimizing exposure to healthy cells. The methods include co-administration of a second therapeutic agent, such as IL-2.

Abstract: The invention features nucleic acid constructs encoding chimeric immunoreceptors (CIRs) that are useful for treating a KIT+ associated disease in patients. In general, the CIRs contain an extracellular domain (e.g., a KIT-ligand (KL) or stem cell factor (SCF)) which interacts with and destroys KIT+ tumor cells, a transmembrane domain, and a cytoplasmic domain for mediating T cell activation (e.g., CD3 zeta and/or the domain of CD28). The invention also features the use of the nucleic acid constructs and/or host cells expressing CIRs in the treatment of a KIT+ associated disease, in particular gastrointestinal stromal tumor (GIST).