Abstract: The invention relates to the field of cancer immunotherapy by employing bicistronic inhibitory chimeric antigen receptor (iCAR)/activating chimeric antigen receptor (aCAR) constructs for use in cancer treatment therapies.

Abstract: The present invention pertains to a novel cell based tumor vaccine platform. The invention provides a method for modifying antigen presenting cells (APCs) to present both MHC class I and/or MHC class II peptides in context of improved peptide presentation protein complexes in order to increase activation of a patient's immune response. In this invention, an MHC II mRNA dendritic cell based vaccine platform was developed to activate CD4+T cells in patients and to enhance the anti-tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP was replaced with an MHCII binding peptide sequences of tumor associated antigens. These chimeric MHC II constructs are presented by APCs and induce proliferation of tumor specific CD4+T cells. The invention provides the constructs, proteins, nucleic acids, recombinant cells, as well as medical applications of these products.

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.