Alloantigen-Activated Lysis of Syngenic Tumor Augmented by Allogenic Lymphocytes as Cold Targets

In the past, most work in tumor immunology involved attempts to demonstrate tumor-specific transplantation antigens; however, recent in vitro work has shown that it is not necessary to sensitize to a specific tumor antigen to achieve lysis of syngenic tumor cells. Responder spleen cells from B6AF₁ mice (H-2a_’b) were sensitized in mixed lymphocyte cultures (MLC) to alloantigens on spleen cells from B10.D2 (H-2d) mice. In cell-mediated lympholysis (CML) assays the relevant allogenic P815 (H-2d) tumor targets and B10.D2 lymphoblast targets were lysed. In addition, the semisyngenic tumor target EL-4 (H-2b) was lysed but RDM-4 (H-2k) was not. B10.BR (H-2k), C57BL/6 (H-2b) and B6AF₁ lymphoblasts were not lysed. If lymphocytes were added as cold targets to the CML assay, B10.D2 lymphocytes completely absorbed lytic activity when B10.D2 lymphoblasts were the target. If B10.D2 lymphocytes were added when P815 was the target, lysis was reduced but could not be abolished. When B10.D2 lymphocytes were added with EL-4 as a target, lysis doubled. These experiments show that the neoplastic determinant on tumor cells recognized by alloantigen-activated lymphocytes does not cross-react with stimulator cell alloantigen and is not an alien histocompatibility antigen. These observations should be considered when in vivo attempts are made to control tumor with in vitro activated lymphocytes; transfer of not only in vitro activated cells but also allogenic stimulator cells to the tumor site may be necessary for maximal tumor destruction.