Disclosed herein are compositions comprising a recombinant nucleic acid sequences encoding a bispecific anti-FSHR T cell engager as well as FSHR-specific CAR molecules, fragments thereof, variants thereof, combinations thereof, and methods of use thereof.

The invention provides improved compositions for adoptive cell therapies for cancers that express CD79A.

The present disclosure provides compositions and methods directed to logic gated CAR-T therapies for treating cancer, such as DIPG, Ewing Sarcoma, and AML, including logic pairs of CAR polypeptides comprising anti-CD56 CAR polypeptides and anti-CD99 CAR polypeptides.

The present disclosure provides compositions and methods directed to logic gated CAR-T therapies for treating cancer, such as DIPG, Ewing Sarcoma, and AML, including logic pairs of CAR polypeptides comprising anti-CD276 CAR polypeptides and anti-CD99 CAR polypeptides.

The present disclosure provides compositions and methods directed to anti-CD99 CAR-T therapies for treating cancer, such as DIPG. Ewing Sarcoma, and AML.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. NK cells have effector activity within the TME, under continuous ligand exposure. NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. We created NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3 to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PDL1+ target cells.

The invention provides recombinant CD47 engager receptor proteins comprising an intracellular domain that enhances an immune response in a cell when the CD47 engager receptor protein binds to CD47 on a target cell. The invention also provides cells comprising the CD47 engager receptor proteins. The CD47 engager receptor protein may be a switched Signal Regulatory Protein Alpha (SIRP) receptor (SIRP switch receptors) and cells that comprise them (SIRP switch cells). SIRP switch receptors recognize CD47 on target tumor cells and transmit an intracellular signal within the SIRP switch cells that upregulates natural killer cell (NK), T cell, and macrophage activity. The result is increased tumor cell killing.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor T-cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CARTs fratricide. CD 1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD 1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD 1a during ontogeny, confining the risk of on-target/off-tumor toxicity. The present invention provides CARs comprising a CD 1a-targeting moiety which may be transduced or transformed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.