Abstract: The compositions and methods described herein are directed to treating solid tumors using CAR T therapy. For example, the compositions include CAR T cells comprising an extracellular domain that binds OR2I1P, LY6G6D, LRRC15, LY6K, GCC, GFRA4, F2RL2, QRFPR, IQGAP3, SIGLEC15, HAVCR1, PSG9, KISS1R, PRAME, HCN4, DPEP3, TMEM270, HER2, SLC7A3, SPRR2F, SLC45A2, CHRM1, CHRNA2, STEAP1B, FCRL2, Luteinizing hormone receptor, EDB, or CLDN18.2.

Abstract: The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. The compositions include CAR comprising an extracellular domain that binds a siglec protein or a receptor that binds the peptide hormone kisspeptin.

Abstract: The present disclosure relates to compositions and methods for treating cancer. For example, a modified cell may include a polynucleotide comprising an NFAT promoter, a nucleotide sequence encoding therapeutic agent, and a nucleotide sequence encoding a VHL-interaction domain of HIF1?, wherein the therapeutic agent comprises, for example, IL-12, IL-6, and/or IFN?.

Abstract: The present disclosure relates to compositions and methods for enhancing T cell response and/or CAR cell expansion and/or maintenance in vivo and/or in vitro. For example, a method of enhancing T cell-based therapy comprises administering genetically modified T cells comprising a first chimeric antigen receptor (CAR) and a second CAR, wherein a binding domain of the first CAR binds a first antigen, and a binding domain of the second CAR binds a second antigen. The first antigen is different from the second antigen. In embodiments, the first CAR binds a surface molecule or antigen of a white blood cell.

Abstract: Embodiments relate to a modified cell comprising a polynucleotide encoding an antigen binding molecule and a polynucleotide encoding an agent targeting one or more extracellular matrix (ECM) molecules. In embodiments, the polynucleotide encoding the agent comprises at least a nucleic acid encoding Cathepsin K (CK), a nucleic acid encoding Neutrophil Elastase (NE), or a nucleic acid encoding MMP7. In embodiments, the nucleic acid encoding NE comprises a nucleic acid encoding NE and a nucleic acid encoding a signaling domain of IL2. In embodiments, expression of the polynucleotide encoding the agent is regulated by hypoxia-inducible factor 1-alpha (HIF1?), nuclear factor of activated T-cells (NFAT), forkhead box P3 (FOXP3), or nuclear factor kappa B (NF-?B).

Abstract: Embodiments of the present disclosure relate to compositions and methods of enhancing anti-tumor activities of modified cells, the method comprising: administering an effective amount of the modified cells to a subject having a solid tumor; and administering an effective amount of an agent to the subject, the agent comprising rapamycin, wherein the modified cells inhibit growth of the solid tumor in the subject, and wherein the anti-tumor activities in the subject are greater than those in a subject that is administered with an effective amount of modified cells but without the agent.

Abstract: The present disclosure relates to compositions and methods for treating cancer. For example, a modified cell may include a polynucleotide comprising an NFAT promoter, a nucleotide sequence encoding therapeutic agent, and a nucleotide sequence encoding a VHL-interaction domain of HIF1?, wherein the therapeutic agent comprises, for example, IL-12, IL-6, and/or IFN?.

Abstract: Embodiments of the present disclosure relate to a polynucleotide encoding a CAR comprising a cytoplasmic domain of CD4, or a CAR comprising SEQ ID NO: 17 in its intracellular domain, and the cytoplasmic domain of CD4 is located between a transmembrane domain of the CAR and a signaling or stimulatory domain, for example, CD3 zeta domain.

Abstract: The present disclosure relates to compositions and methods of treating a subject having digestive tract cancer, the method comprising: administering an effective amount of a composition to the subject, the composition comprising a first population of cells comprising a first CAR binding a first antigen, and a second population of cells comprising a second CAR binding GCC, wherein the first antigen comprises a cell surface molecule of a white blood cell (WBC).

Abstract: The present disclosure describes compositions and methods for treating solid tumors expressing mesothelin (MSLN) using chimeric antigen receptor (CAR) T cell therapy. The compositions comprise CARs with an extracellular domain that specifically binds MSLN. The extracellular domain comprises a single variable domain (VHH) antibody that targets MSLN. Polynucleotides encoding the anti-MSLN CAR constructs are provided. Pharmaceutical compositions comprising CAR T cells expressing the anti-MSLN CARs are also described. The CAR T cells demonstrate cytotoxicity against MSLN-expressing tumor cells in vitro and anti-tumor activity in vivo. Methods are provided for generating the CAR T cells by transfecting T cells with lentiviral or retroviral vectors carrying anti-MSLN CAR encoding sequences. The anti-MSLN CAR T cell therapy described herein provides an effective approach for treating solid tumors expressing MSLN, such as mesothelioma, ovarian cancer, pancreatic cancer, and lung cancer.

Abstract: The compositions and methods described herein are directed to treating solid tumors using CAR T therapy and/or antibodies targeting GCC. The compositions include CAR comprising an extracellular domain that binds GCC.

Abstract: The present disclosure describes compositions and methods for treating cancer. Embodiments relate to a cell modified to express one or more molecules at a level that is higher or lower than the level of the one or more molecules expressed by a cell that has not been modified to express the one or more molecules, wherein the one or more molecules comprise Cavin3, ZBED2, and MYC.

Abstract: The present disclosure relates to compositions and methods for enhancing infiltration of lymphocytes into tumor tissue, enhancing anti-tumor lymphocyte activities in tumor microenvionment (TME), inhibiting regulatory lymphocyte (e.g., B and T cells) activities in TME, and/or long term benefit of cell therapies. For example, in a method of in vivo cell expansion, the method comprises administering an effective amount of cells comprising an antigen binding molecule to a subject; and administering an effective amount of presenting cells expressing a solid tumor antigen that the binding molecule binds.

Abstract: The present disclosure relates to compositions and methods for reducing side effects and/or enhancing cancer treatment that use modified immune cells expressing chimeric antigen receptors (CARs) or modified T cell receptors (TCRs). The modified immune cells, such as T cells or NK cells, can express CARs or TCRs targeting solid tumor antigens, white blood cell antigens like CD19, or bispecific CARs/TCRs targeting both. The methods include administering dasatinib to reduce the side effects associated with CAR T or TCR therapy and/or enhance cancer treatment. The modified cells can co-express additional therapeutic agents like cytokines.

Abstract: The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. For example, the compositions include CAR T cells comprising an extracellular domain that binds FCR1, MSLN, GPC-3, ALPP, CD70, CLDN6, ROR1, CD205, ACPP, ADAM12, or CLDN18.2.

Abstract: Embodiments relate to a modified cell engineered to comprise a modified TCR-CD3 complex, wherein the CD3?, ?-chain, CD3?, and/or CD3? chains of the modified TCR-CD3 complex are linked to one or more co-stimulatory signaling domains.

Abstract: Embodiments relate to a modified cell comprising a polynucleotide encoding a dominant negative form of Death receptor 5 (DR5). In embodiments, the modified cell further comprises a chimeric antigen receptor (CAR) and/or a modified TCR.

Abstract: The present disclosure relates to a fusion protein and uses thereof. For example, the fusion protein comprises an extra-cellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain is derived from a first molecule, and the intracellular domain is derived from a second molecule. The first molecule is different from the second molecule, and the second molecule comprises OX40, CD40, 4-1 BB, GITR, ICOS, CD28, CD27, HER2, EGFR, EL-10R, IL-12R, IL-18R1, IL-23R, GP130, or IL-15Ra.

Abstract: The present disclosure relates to compositions and methods for treating a subject having cancer associated with melanoma-associated antigen 4 (MAGE-A4) peptide. The disclosure includes the embodiments relate to a chimeric antigen receptor (CAR) that binds MAGE-A4 peptide, a polynucleotide encoding a CAR that binds the MAGE-A4 peptide, a modified cell comprising a CAR that binds the MAGE-A4 peptide, and a population of modified cells comprising a CAR that binds the MAGE-A4 peptide.

Abstract: The present disclosure relates to compositions and methods for enhancing T cell response in vivo. For example, a method of enhancing T cell response in a subject or treating a subject having cancer, the method comprising: administering an effective amount of a composition comprising modified cells to the subject having a form of cancer associated with or expressing an antigen, for example, a solid tumor antigen; and administering (1) a nucleic acid encoding the antigen, (2) additional modified cells comprising the nucleic acid or the antigen, or (3) microorganisms, for example cold viruses, comprising the nucleic acid or the antigen. In embodiments, the modified cells comprise mixed cells targeting a solid tumor antigen and a white blood cell (WBC) antigen. In embodiments, the modified cells comprise a dominant negative form of an immune checkpoint molecule (e.g., PD-1). In embodiments, the modified cells comprise an exogenous polynucleotide encoding a therapeutic agent, such as IL-12 and IFN?.