Abstract: Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b)a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

Abstract: Provided herein are methods for detecting an antigen or for detecting expression of a chimeric antigen receptor (CAR). The methods include obtaining a sample from a subject, contacting the sample with a fusion protein comprising a reporter fused to a single chain antibody specific to the antigen or fused to an extracellular domain of an antigen targeted by the CAR or fused to Protein L and assaying the activity of the reporter, wherein presence of reporter activity or increase in reporter activity relative to a reference value is indicative of presence of the antigen or presence of the expression of the chimeric antigen receptor in the sample.

Abstract: Provided herein are methods for detecting an antigen or for detecting expression of a chimeric antigen receptor (CAR). The methods include obtaining a sample from a subject, contacting the sample with a fusion protein comprising a reporter fused to a single chain antibody specific to the antigen or fused to an extracellular domain of an antigen targeted by the CAR or fused to Protein L and assaying the activity of the reporter, wherein presence of reporter activity or increase in reporter activity relative to a reference value is indicative of presence of the antigen or presence of the expression of the chimeric antigen receptor in the sample.

Abstract: The disclosure relates to compositions and methods of generating synthetic antigen receptors or SAR (e.g., SIR, zSIR, cTCR, ab-TCRs, AABD-TCRs, TFP, TACs etc.) and antibodies (e.g., bispecific antibodies, DARTs etc.) comprising one or more novel antigen binding domains. SARs as described comprise single chain immune receptors (e.g., 1st, 2nd and 3rd generation chimeric antigen receptors, TFPs. Tri-TAC and the like) and multiple chain immune receptors (e.g., SIR, zSIR, cTCR. ab-TCR. AABD-TCR. ??TFP, ydTFP, recombinant TCRs etc.). SARs are able to redirect immune cell specificity and reactivity toward one or more selected targets exploiting the antigen-binding domain properties.

Abstract: The disclosure provides compositions and method that promote adoptive cellular therapy. The disclosure provides polynucleotides, vectors, systems and cells comprising chimeric antigen receptors (CARs), synthetic immune receptors (SIRs), and the like in combination the specific activators of NFkB activity, thus improving cellular proliferation, expression and reduced apoptosis, which improves cell persistence in adoptive cell therapy.

Abstract: The present disclosure relates to methods for preventing, ameliorating or treating complications caused by a viral infection (e.g., SARS, SARS-cov2, MERS, Influenza etc.), by administration of an immune response modulating agent (IRMA).

Abstract: Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

Abstract: Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

Abstract: Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

Abstract: The disclosure provides synthetic immune receptors (SIRs), nucleic acids encoding the SIRs, methods of making and using the SIRs, in, for example, adoptive cell therapy.

Abstract: Described herein are novel compositions and methods to improve the safety and efficacy of adoptive cellular therapies of cancer, infection, allergic, degenerative and immune disorders. The disclosure provides a) novel methods and compositions to reduce the accidental insertion of chimeric receptors into cancer cells; b) novel methods to measure the titer of viral vectors; c) novel compositions to generate antigen masking receptors and methods to use such receptors to protect normal cells from immunotherapeutic agents; d) novel compositions and methods to extend the life-span of allogeneic cells, including allogeneic CAR-T cells; e) novel compositions and methods to ameliorate the side-effects of cellular therapies and f) novel compositions of Synthetic Immune Receptors and Ab-TCRs with mutant TCR? constant chains.

Abstract: Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

Abstract: The disclosure relates generally to the generation and use of immune effector cells (e.g., T cells, NK cells) engineered to express an immune receptor (e.g., Chimeric Antigen Receptor, Synthetic Immune Receptor, T Cell Receptor etc.) to treat a disease associated with expression of a target antigen.

Abstract: The disclosure provides diverse antigen binding domains and platforms for construction of conventional and next generation chimeric antigen receptors for adoptive cellular therapies for cancer, infection, allergic, degenerative and immune disorders, Also provided are approaches for activation and expansion of immune T cells for adoptive cellular therapies for cancer, infection, allergic, degenerative and immune disorders.

Abstract: Described herein are methods for assessing cytotoxicity of an agent. The methods include providing a target cell that has been engineered to express intracellularly a reporter that is not expressed endogenously by the target cell, exposing the target cell to an agent capable of modulating cytotoxicity and assaying the activity of the reporter, wherein a change in reporter activity relative to a reference value is indicative of the agent being able to modulate cytotoxicity of the target cell.

Abstract: Described herein are methods for selecting lymphocytes for adoptive cell therapy based on P-glycoprotein expression and compositions comprising same.

Abstract: Provided herein is a composition comprising, a cell, comprising nucleic acids encoding a chimeric antigen receptor (CAR) and one or more of signaling proteins selected from K13-vFLIP, MC159-vFLIP, cFLIP-L, cFLIP-p22, HTLV1-Tax and HTLV2-Tax, wherein the CAR comprises an a) extracellular antigen specific domain, b) a transmembrane domain and c) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM); wherein c) is located at the C-terminus of the chimeric receptor. In some embodiments, the CAR further comprises one or more co-stimulatory domains. Also provided herein are methods for treating diseases using the compositions described herein.

Abstract: Provided herein are methods for detecting an antigen or for detecting expression of a chimeric antigen receptor (CAR). The methods include obtaining a sample from a subject, contacting the sample with a fusion protein comprising a reporter fused to a single chain antibody specific to the antigen or fused to an extracellular domain of an antigen targeted by the CAR or fused to Protein L and assaying the activity of the reporter, wherein presence of reporter activity or increase in reporter activity relative to a reference value is indicative of presence of the antigen or presence of the expression of the chimeric antigen receptor in the sample.

Abstract: Methods for treating primary effusion lymphoma (PEL) are provided. The methods include administering to a patient in need thereof an effective amount of an immunomodulatory compound. Suitable immunomodulatory compounds include compounds having the formula: wherein X in Formula IV may be independently selected from the group that includes hydrogen, a halide, an aliphatic group and an amine group.

Abstract: Methods for treating primary effusion lymphoma (PEL) are provided. The methods include administering to a patient in need thereof an effective amount of an immunomodulatory compound. Suitable immunomodulatory compounds include compounds having the formula: wherein X in Formula IV may be independently selected from the group that includes hydrogen, a halide, an aliphatic group and an amine group.