Induction of Cell-Mediated Immunity Against Leukemia EL4 in C57BL Mice 1,2

SUMMARY-The subcutaneous growth of leu-kemia EL4 in C57BL mice was suppressed when the tumor cells were mixed with immune BALBjc anti·EL4 peritoneal exudate lymphoid cells before injection into C57BL mice. The protected mice showed increased resistance to a subsequent subcutaneous or intraperi· toneal challenge with EL4 tumor cells alone. Effector cells of C57BL origin and cytotoxic for EL4 tumor cells in vitro were detected in the peritoneal cell exudate and also prevented subcutaneous EL4 tumor growth in C57BL mice. These experiments demonstrated a means for the induction of cellular immunity against a lethal tumor in susceptible hosts.-J Natl Cancer Inst 51: 1877-1882, 1973. ATTEMPTS to produce immunity to the C57BL leukemia EL4 in susceptible recipients by tumor excision (1) or injection of X-irradiated tumor cells (2) have not succeeded. C57BL mice failed to reject EL4 tumor cells despite the presence of a circulating cross-reactive antibody cytotoxic to the tumor (3). Chemical alteration of EL4 cells with concanavalin A or dinitrophenylaminocaproate somewhat in-creased immunogenicity, as measured by the pro-duction of C57BL cells cytotoxic for EL4 in vitro, but did not increase protection of animals against in vivo challenge by the tumor cells (2). Immune lymphoid cells retarded the growth of EL4 when administered with EL4 tumor cells to susceptible or resistant recipients (4, 5). We demonstrate here that subcutaneous (sc) administration of BALB/c anti-EL4 peritoneal exudate lymphoid cells together with EL4 markedly increases the resistance of C57BL mice to further challenge with the tumor cells alone; and we show that this increased resistance is due to a cellular immune response against the tumor. MATERIALS AND METHODS Animals.-We used 2- to 4-month-old mice of the following strains: C57BL/Spr (Roswell Par