Abstract: The present disclosure relates to compositions and methods for compositions, methods, and kits for treating cancer using chimeric antigen receptor (CAR) modified cells. Some embodiments of the present disclosure relate to an isolated nucleic acid sequence encoding CAR. The CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. The antigen binding domain may bind to an antigen of a non-essential organ.

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: The present disclosure relates to compositions and methods for enhancing CAR T therapy through uses of co-stimulation. Some embodiments relate to an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR) and an agent associated with a co-stimulatory molecule, the CAR comprising an intracellular domain of a costimulatory molecule.

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 modified cell comprising a polynucleotide encoding a secretable scFv binding SIGLEC-15 and/or encoding a dominant negative form of CD44. In embodiments, the modified cell further comprises an antigen-binding molecule, which for example, is a CAR comprising an antigen-binding domain, a transmembrane domain, and an intracellular signaling domain.

Abstract: Embodiments relate to compositions and methods for treating solid tumors. For example, the compositions comprise modified cells comprising an isolated polynucleotide comprising a polynucleotide encoding a nuclear factor of activated T cells (NFAT) promoter operatively associated with a polynucleotide encoding FLT3L.

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: Embodiments relate to a modified cell comprising a chimeric antigen receptor (CAR) and a dominant negative form of PD-1, wherein the dominant negative form of PD-1 lacks a functional PD-1 intracellular domain for PD-1/PD-L1 signal transduction, and the CAR comprises an antigen binding domain, a transmembrane domain, a co-stimulatory domain, and a CD3 zeta domain. The dominant negative form of PD-1 is regulated by an inducible gene expression system.

Abstract: Embodiments of the present disclosure relate to compositions and methods of enhancing lymphocytes' ability to treat cancer patients. Embodiments relate to a polynucleotide comprising a nucleic acid encoding a chimeric antigen receptor (CAR), a nucleic acid encoding an Oxygen-Dependent Degradation domain (ODD), and a nucleic acid encoding one or multiple sequences of Hypoxia-Response Element (HRE).

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?.

Abstract: Embodiments relate to a modified cell comprising an antigen binding molecule, and the expression and/or function of one or more genes in the modified cell has been enhanced or reduced or eliminated. The one or more genes include CXCR3, SLC1A3, YAP, TIGIT, S1P1, and IL-35. In embodiments, the cell is a T cell, a dendritic cell, a NK cell, or a macrophage cell. In embodiments, the antigen binding molecule comprises a chimeric antigen receptor (CAR) and/or the second antigen binding molecule is a T Cell Receptor (TCR).

Abstract: Embodiments of the present disclosure include a method for treating Systemic Lupus Erythematosus (SLE) using CD19 CAR T cells. The method includes administering to the human patient a pharmaceutically effective amount of a population of T cells of the human patient that express a chimeric antigen receptor (CAR) that comprises the amino acid sequence of, e.g., SEQ ID NO: 23.

Abstract: The present disclosure relates to a system for immune therapy, the system comprising a sample processing module configured to obtain whole blood from a subject; a cell incubation module configured to activate blood cells of the whole blood and/or introduce a vector into the blood cells of the whole blood; and a cell infusion module configured to infuse at least a portion of the whole blood to the subject, wherein the blood cells comprise CD3+ cells, NK cells, myeloid cells, and neutrophils.

Abstract: The present disclosure relates to compositions and methods for enhancing cell response and/or expanding chimeric antigen receptor (CAR) cells and/or maintenance in vivo and/or in vitro. In embodiments, the method comprises obtaining CAR T cells comprising a CAR comprising a binding domain that binds a solid tumor antigen, a transmembrane domain, and an intracellular domain; and contacting the CART cells with white blood cells and a bispecific antibody, such as a Bispecific T cell engager (BiTE®), thereby activating the CAR T cells, wherein the level of activation of the CAR T cells is higher than the level of activation of CAR T ells that are contacted with B cells without the bispecific antibody. The bispecific antibody comprises a first binding domain binding CD3 and a second binding domain binding CD19, CD20, CD22, or BCMA.

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?.

Abstract: Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.