Disclosed herein are cells including cells expressing CD24 and related methods of their use and generation. In some embodiments, the cells disclosed herein do not express one or more MHC I and/or MHC II human leukocyte antigens. In some embodiments, the cells are hypoimmunogenic.

Disclosed herein are CAR-T cells engineered to express mutant PGC-1α, wildtype NT-PGC-1α, or mutant NT-PGC-1α to enhance or prevent degradation of metabolic fitness. Also disclosed herein is a method for enhancing metabolic fitness of a CAR-T cell by transducing the CAR-T cell with a vector encoding a mutant PGC-1α, wildtype NT-PGC-1α, or mutant NT-PGC-1α. Also disclosed is a method for producing CAR-T cells that involves transducing activated T cells with a viral vector encoding a mutant PGC-1α, wildtype NT-PGC-1α, or mutant NT-PGC-1α polypeptide.

Provided for herein in several embodiments are immune cell-based compositions comprising BCMA-directed chimeric antigen receptors (CAR). In several embodiments, the immune-cell based compositions also target an additional tumor marker and/or an additional epitope of BCMA. In several embodiments, the BCMA-directed CAR is expressed in a Natural Killer cell. In several embodiments, combinations of BCMA-CAR-expressing NK cells are administered in conjunction with, for example CAR-expressing NK cells and/or CAR-expressing T cells that are directed to an additional cancer marker and/or an additional epitope of BCMA. Also provided for herein are methods and uses of the chimeric antigen receptors in immunotherapy.

The present disclosure relates to polynucleotides encoding a chimeric polypeptide comprising a c-Jun polypeptide, a ROR1-binding protein, and a truncated EGF receptor. Also provided are cells (e.g., T cells) expressing CARs comprising a ROR1-binding protein and overexpressing a c-Jun polypeptide. Overexpression of c-Jun in CAR T cells confers improved properties, e.g., reducing or preventing exhaustion.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.

The present disclosure relates to the pharmaceutical field. More specifically, it relates to methods for treating a tumor in a human subject in need thereof, said method comprising administering a therapeutically efficient amount of an anti-BTN3A antibody which induces the activation of Vγ9Vδ2 T cells, in combination with a therapeutically efficient amount of an anti-PD1/PDL1 treatment, wherein said subject is having relapsed or refractory tumors to anti-PD1/PDL1 treatment.

The present disclosure provides synthetic modular polypeptide libraries and nucleic acids encoding such synthetic modular polypeptide libraries. Also provided are methods of making synthetic modular polypeptide libraries and nucleic acids encoding synthetic modular polypeptide libraries. Methods of screening a synthetic modular polypeptide library to identify a selected phenotype associated with a member of a synthetic modular polypeptide library are also provided where such methods find use in both in vitro and in vivo assays.

Methods and compositions for treating cancer are provided. Compositions comprising ceramide nanoliposomes are administered to a subject in need of such treatment. The composition administration also enhances immunotherapy. Further administering compositions in combination with tumor antigen specific T-cells, and/or compositions in combination with tumor antigen expressing cells, and/or said compositions in combination with antagonists of PD-1 provides for enhanced results. Administration of the compositions provides for effective treatment of tumors including regression and eradication of established tumors.