Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

Disclosed herein are methods for treating cancer comprising administering CAR-modified immune cells and at least one Retinoic Acid Receptor agonist.

The disclosure features immune cell delivery lipid nanoparticle (LNP) compositions that allow for enhanced delivery of agents, e.g., nucleic acids, such as therapeutic and/or prophylactic RNAs, to immune cells, in particular T cells, as well as B cells, dendritic cells and monocytes. The LNPs comprise an effective amount of an immune cell delivery potentiating lipid such that delivery of an agent by an immune cell delivery LNP is enhanced as compared to an LNP lacking the immune cell delivery potentiating agent. Methods of using the immune cell delivery LNPs for delivery of agents, e.g., nucleic acid delivery, for protein expression, for modulating immune cell activity and modulating immune responses are also disclosed.

Chimeric antigen receptors containing CD33 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Disclosed are off-the-shelf immune effector cells that are engineered to express anti-CD3 antibodies disclosed herein that are configured to autoactivate the immune effector cells, thereby decreasing expression of T cell receptors (e.g. TCR??) that could result in GVHD. Also disclosed are methods for modifying donor immune effector cells to make them suitable for off-the-shelf treatment of allogeneic subjects. These methods involve engineering the cells to express an anti-CD3 antibody configured to activate the cells. In some embodiments, the antibody is a bi-specific antibody that binds the CD3 complex on the immune effector cells. In other embodiments, the antibody is a membrane bound anti-CD3 antibody that autoactivates the immune effector cell.

Disclosed herein are methods of producing tumor antigen-specific T cells and uses thereof. In the present method, peripheral blood mononuclear cells (PBMCs) isolated from a subject are cultivated with bi-specific antibodies (BsAbs) in a culture medium so as to produce the tumor antigen-specific T cells from the PBMCs. Also provided in the present disclosure are tumor antigen-specific T cells produced by the present method, and uses thereof in treating subjects suffering from cancers.

The technology described herein is directed to compositions comprising components of multi-component CALs or CARs, e.g., a TCR recognition domain; and one or both of: (a) an intracellular signaling domain; and (b) a first-type protein interaction domain. Further provided herein are methods for treating or preventing an autoimmune disease, a transplant rejection, or graft versus host disease.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.

Disclosed herein are methods for culturing CAR-modified immune cells with at least one Retinoic Acid Receptor and/or Retinoid X Receptor active agent.