In vivo growth inhibition of Ia+ lymphomas in SJL mice treated with I-As-reactive monoclonal antibody

Abstract

SJL/J mice injected with a syngeneic, I-As-positive transplantable lymphoma (RCS) and treated with I-As-reactive monoclonal antibody (McAb) for one week showed reduced tumor growth in peripheral lymph nodes and spleen when compared to untreated controls. The effect of McAb on RCS growth was observed after treatment with I-As McAb derived from two different hybridomas, but similar growth inhibition did not occur in RCS-injected mice treated with a non-cross-reacting I-Ab McAb. Specificity of the effect was also indicated by the observation that partial absorption of I-As McAb with I-As-positive cells decreased its ability to reduce tumor growth in RCS-injected SJL recipients. In parallel experiments in which McAb treatment was stopped after one week, RCS-injected mice survived up to 8 times longer (80 days) than untreated control mice, which died by day 10 after tumor cell inoculation. Although the precise mechanism(s) by which McAb treatment influences RCS growth has not been fully characterized, it is likely that I-As McAb may block the characteristic T cell proliferative response to I-A antigens on RCS cells that appears necessary for progressive tumor growth in vivo. Absence of such host immune recognition could result in either a deficiency in production of RCS growth-promoting lymphokines or induction of effector cells capable of inhibiting tumor growth.