The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).

Nucleic acid molecules encoding an IL-15 domain and a chimeric antigen receptor (CAR) that targets cells expressing prostate stem cell antigen are provided as well as polypeptides encoded thereby. Vectors and host cells such as immune cells containing the nucleic acid molecules also are disclosed, as well as methods for their use.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

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.

The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising a chimeric antigen receptor (CAR) capable of binding human PSCA. CARs capable of binding human PSCA, and nucleic acids encoding the same are also provided. Provided herein are bispecific CARs capable of binding human PSCA and human PSMA, nucleic acids encoding the same, and modified immune cells comprising the same. Modified immune cells comprising a PSMA CAR and a PSCA CAR are also provided. Compositions and methods of treatment are also provided.

Compositions and methods are disclosed herein for producing one or more immunoglobulins in an isolated cytotoxic B lymphocyte cell line. An isolated cell line includes an isolated B lymphocyte cell line capable of expressing at least one exogenously incorporated membrane immunoglobulin capable of binding to a first antigen and at least one endogenous secreted immunoglobulin capable of binding to a second antigen, and further capable of expressing at least one exogenously incorporated recombinant B cell receptor that signals for expression of cytotoxic effector molecules.

The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).

Provided are a preparation method for a CTL cell and an application thereof. The preparation method comprises the following steps of: inducing a CTL cell by using a tumor antigen PAP-GM-CSF sensitized DC cell; and knocking out a PD-1 gene of the CTL cell to obtain a PD-1 knock-out CTL cell. The CTL cell obtained by the preparation method can be used for preparing drugs for treatment of prostate cancer, especially for treating PAP-positive prostate cancer. The CTL cell does not cause CTL cell failure and anergy due to the tumor-expressed PD-L1 after being transfused into the body, thereby producing efficient specific cytotoxic effect on a tumor cell and improving the curative effect and reducing the side effect.

Embodiments of the present invention provide isolated proteins comprising antigen binding domains that bind kallikrein related peptidase 2 (hK2), including monospecific and bispecific antibodies. Additional embodiments of the invention provide polynucleotides encoding the hk2-specific proteins, vectors, host cells, and methods of making and using them.

Embodiments of the disclosure include methods and compositions that allow for development of efficient chimeric antigen receptors (CARs) by selecting appropriate spacer content and/or length by balancing the effects of tonic signaling with the efficacy of antigen recognition for the spacer. In specific embodiments, the CH3 domain from IgG2 is utilized as a spacer. In specific embodiments, T cell metabolic activity is utilized as a measure of tonic signaling to facilitate determination of suitable CAR constructs. In other embodiments, cells bearing chimeric Fc receptor target molecules are utilized to target Fc gamma receptor (FcR)-bearing for the purpose of their destruction.