(A) Endogenous T cells express a single heterodimeric TCR. (B) Bispecific T cells are created by the introduction of genes that encode proteins that recognize antigens expressed by target tumor cells. These genes can encode natural TCRs that function in the same MHC-restricted manner as endogenous TCRs but have tumor antigen specificity. (C) Alternatively, these genes can encode chimeric tumor antigen–specific receptors, or T bodies, that target surface antigens in an MHC-independent fashion. T bodies express an extracellular ligand generally derived from an antibody and intracellular signaling modules derived from T cell–signaling proteins. LAT, linker for activation of T cells; ScFv, single chain variable fragment; ZAP70, ζ-chain–associated protein kinase 70 kDa.