Compositions and methods for immunotherapy

A method of inducing tumor cell death in a subject, and/or treating a neoplasm, treating a pathogen infection in a subject, and/or treating an autoimmune disorder, the method comprising administering to the subject an immunoresponsive cell or a pharmaceutical composition comprising the immunoresponsive cell, wherein the immunoresponsive cell comprises:

• a) a chimeric antigen receptor (CAR) that binds to a first antigen with a dissociation constant (Kd) of about 5×10−8 M or more, wherein binding of the CAR to the first antigen is capable of delivering an activation signal to the immunoresponsive cell, and
• b) a chimeric co-stimulating receptor (CCR) that binds to a second antigen, wherein binding of the CCR to the second antigen is capable of delivering a costimulatory signal to the immunoresponsive cell but does not alone deliver an activation signal to the immunoresponsive cell,
• wherein the immunoresponsive cell is capable of i) exhibiting negligible cytolytic activity against cells that are singly positive for the first antigen, and ii) inducing cytolytic activity against cells that are positive for both the first and second antigens.