Abstract: Among the various aspects of the present disclosure is the provision of methods to predict the risk of developing immunotherapy-associated neurotoxicity in a subject by measuring neurofilament light chain (NfL) levels in a biological sample obtained from the subject, wherein the subject is receiving or may receive an immunotherapy such as CAR T cell therapy.

Abstract: Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Abstract: Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1/JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the JAK inhibitor is selected from baricitinib. In some embodiments, the method comprises administering a cancer therapeutic.

Abstract: Disclosed herein are methods of genome-editing and transduction of T cells and methods of immunotherapy in using them. In particular, the disclosure relates to engineered chimeric antigen receptor (CAR)-bearing T cells and methods of using the same for the treatment of cancer.

Abstract: Disclosed herein are genome-edited chimeric antigen receptor T cells (CAR-T), which can be derived from a cytotoxic T cells, a viral-specific cytotoxic T cell, memory T cells, or gamma delta (??) T cells, and comprise one or more chimeric antigen receptors (CARs) targeting one or more antigens, wherein the CAR-T cell is deficient in one or more antigens to which the one or more CARs specifically binds. In particular, the present disclosure relates to engineered mono, dual, and tandem chimeric antigen receptor (CAR)-bearing T cells (CAR-T) and methods of immunotherapy for the treatment of cancer.

Abstract: Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Abstract: Disclosed herein are genome-edited invariant natural killer T (iNKT) cells and methods of immunotherapy using them. In particular, the disclosure relates to engineered chimeric antigen receptor (CAR)-bearing INKT cells (CAR-iNKTs) and methods of using the same for the treatment of cancer.

Abstract: The present disclosure provides therapeutic agents including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such therapeutic agents. Methods of using the therapeutic agents are also provided. The present disclosure further provides combinations of a VLA-4 inhibitor and an agent which interacts with a chemokine receptor, and methods of use thereof. In some embodiments, the disclosed combinations may be used in a method of mobilizing hematopoietic stem cells. In some embodiments, the disclosed methods may be used in the treatment of a condition which requires the collection of hematopoietic stem cells for transfusions or in chemotherapy. The present disclosure further provides methods of treating a patient comprising administering an agent which interacts with a chemokine such as G-CSF, plerixafor, or Gro-? and VLA-4 inhibitors.