Abstract: The invention provides methods or compositions for treating cancer using an immune cell, e.g, a T-cell, e.g., a CAR T-cell, optionally in combination with a superantigen conjugate. The invention also provides methods for making immune cells, e.g, T-cells, e.g, CAR T-cells, for use in the treatment of cancer.

Abstract: The present invention provides a method for identifying a target pair comprising i) an inhibitory chimeric antigen receptor (iCAR) or a protective chimeric antigen receptor (pCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR or pCAR target is directed to a target extracellular polymorphic epitope, and ii) an activating chimeric antigen receptor (aCAR), wherein the aCAR is directed to a target non-polymorphic cell surface epitope of a protein, as well as methods of making and use of such pairs in the treatment of cancer.