The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor. It relates to cells comprising: an antigen-recognizing receptor (e.g., a chimeric antigen receptor, a TCR, or a TCR like fusion molecule), a Fas ligand polypeptide (FasL), and a gene disruption of a Fas locus. The gene disruption of the Fas locus can improve the activity and/or efficiency of the cells. The presently disclosed cells, compositions, and methods can be used in allogeneic settings.

The present invention concerns methods and compositions related to T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. In aspects of the invention, T cells that are CD70-specific are employed. In particular aspects, there are T cells expressing a novel molecule that comprises the full-length CD70 receptor (CD27) fused to the zeta signaling domain of the T-cell receptor complex. Such T cells recognized CD70-positive tumor cells and have cytolytic activity against CD70-positive cancer cells.

The disclosure provides CARs (CARs) that specifically bind to CD70. The disclosure further relates to engineered immune cells comprising such CARs, CAR-encoding nucleic acids, and methods of making such CARs, engineered immune cells, and nucleic acids. The disclosure further relates to therapeutic methods for use of these CARs and engineered immune cells comprising these CARs for the treatment of a condition associated with malignant cells expressing CD70 (e.g., cancer).

The present invention provides methods compositions and methods of preparing autologous B-cells that secrete a monoclonal of interest useful in immunotherapy.