The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The present disclosure relates to treating a subject comprising administering to the subject a therapy (e.g., a cell therapy, e.g., an adoptive cell therapy, e.g., a CAR-T cell therapy), wherein, prior to the administration, the subject has been preconditioned with a personalized amount of a chemotherapeutic agent. The personalized amount provides an optimal exposure to the chemotherapeutic agent.

Provided herein is a method of treating a subject who has multiple myeloma. A single infusion of chimeric antigen receptor (CAR)-T cells comprising an anti-BCMA CAR comprising a polypeptide is administered to the subject. In certain embodiments, the dose of CAR-T cells administered to the subject is from 1.010.sup.5 to 5.010.sup.6 of CAR-T cells per kilogram of the subject's mass. The method of treatment is effective in obtaining and maintaining minimal residual disease negativity status, as well as other beneficial clinical outcomes related to efficacy and safety.

Disclosed herein are polypeptides, such as monoclonal antibodies (mAbs) and functional fragments thereof, synthetic antigen-binding proteins such as single-chain variable fragments (scFvs), and chimeric antigen receptors (CARs), that can specifically recognize tumor-associated antigens (TAAs) on cancer cells, for example those that express CD33, FLT3, and CLL-1, useful in the treatment of diseases such as cancer.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

Methods of using polypeptides to modulate transforming growth factor-? (TGF?) signaling (e.g., TGF? receptors, antibodies or antigen-binding fragments thereof that specifically bind TGF? or a TGF? receptor) are provided. Compositions comprising the antibodies or fragments thereof and methods of using the same for treatment of diseases involving TGF? activity are provided. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions comprising these antigen binding agents and fragments thereof are also disclosed. The invention also provides therapeutic methods for utilizing the TGF? signaling modulators are provided herein.

This disclosure relates to compositions and methods for treating cancer using chimeric antigen receptor T cells and/or antigen binding domains targeting CLDN18.2.

In certain aspects, provided herein are compositions and methods for treating cancer. The methods of the present disclosure comprise administering to a subject in need thereof a NK cell expressing a CAR in combination with an antigen-binding molecule that binds to a tumor antigen, wherein the CAR-NK cell targets tumor cells through binding to the antigen-binding molecule.

A novel chimeric receptor composition, a recombinant vector, a cell, and an application thereof. The novel chimeric receptor composition includes a conventional chimeric antigen receptor (CAR), and a NKG2D chimeric receptor including a full-length sequence or a truncated fragment of NKG2D, DAP10, and/or DAP12, referred to as a SNR-armed CAR. The chimeric receptor composition enables a conventional CAR-T cell to express a NKG2D extracellular domain and an intracellular signal domain, expands a CAR-T antigen recognition spectrum, solves the tumor heterogeneity, achieves a lower level of cytokine release while enhancing the killing capability of CAR-T on tumor cells expressing target antigens, reduces the possibility of cytokine storm occurrence, and improves the CAR-T security.

Disclosed herein are methods and compositions for cell-based immunotherapies that simultaneously target the tumor microenvironment (TME) via NKG2D ligands and tumor cells via tumor-associated antigens, specifically using immune effector cells as the platform due to their reduced toxicity against normal tissue. In some embodiments, immune effector cells co-express an NKG2D cytotoxic CAR and a CAR directed against a tumor-associated antigen that provides costimulatory signals to the immune effector cell, thus killing only in the presence of both antigens specifically within the TME. In contrast, within normal tissue that might express the tumor-associated antigen, but where self-HLA is also expressed, the costimulatory signal by itself is insufficient for immune effector cell activation, thereby preventing off-tumor toxicity.