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: 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 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: 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 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: Embodiments relate to a modified T cell comprising an antigen binding molecule, wherein expression and/or function of CDC42 in the modified cell has been enhanced. In embodiments, the modified cell has an increased level of cytokine release in response to an antigen that the antigen binding molecule binds as compared to a corresponding T cell that does not overexpress CDC42. In embodiments, the cytokine release comprises a cytokine release of IFN?. In embodiments, the modified cell has an enhanced migration capability in response to a chemokine as compared to a corresponding T cell that does not overexpress CDC42.

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 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 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: A logistics system for managing a network of independent delivery partners may include models to detect delivery defects. The models may generate defect scores for each onboarded delivery partner. The system may collect delivery data to continuously update the models. The updated models may score delivery partners for early detection of delivery defects and determine remediations steps. The system may train one or more models to determine the scores based on a terminating step of the delivery steps. The scores may indicate a likelihood the terminating step was caused by intentional action or by accident. The system may determine remediations steps based on the likelihood of intentional action.