CROSS-REACTIVITY OF ANTI-CD3 IL-2 ACTIVATED EFFECTOR-CELLS DERIVED FROM LYMPH-NODES DRAINING HETEROLOGOUS CLONES OF A MURINE TUMOR/

Cells from lymph nodes (LN) draining progressively growing tumors can differentiate into immune effector cells upon in vitro stimulation wit h anti-CD3 monoclonal antibodies followed by interleukin-2. The adopti ve transfer of these activated LN cells to tumor-bearing mice mediates potent tumor-specific therapeutic effects. In this study, we sought t o further characterize the antitumor efficacy and specificity mediated by the anti-CD3/IL-2 activated tumor-draining LN cells against hetero logous clones derived from the murine MCA 106 sarcoma. Ten clones of d ivergent characteristics with regard to morphology, in vivo growth rat e, ability to establish pulmonary metastases, MHC class I (H-2) antige n expression, susceptibility to lysis by allogeneic cytotoxic T-lympho cytes, as well as sensitivity to doxorubicin were selected and analyze d. In adoptive immunotherapy experiments, pulmonary metastases derived from each clone were found to be sensitive to the therapeutic effects of activated cells derived from LN draining the parental MCA 106 tumo r. The antigenic cross-reactivity was evident from the observation tha t activated cells from LN draining each of the individual tumor clones were capable of mediating the regression of parental tumor metastases . The specificity of the antitumor reactivities mediated by LN cells d raining MCA 106 clones was demonstrated by a lack of in vivo efficacy against metastases derived from the antigenically distinct MCA 205 sar coma. Additionally, selected clones were tested for their ability to s timulate draining LN against other cloned tumors or used as targets fo r therapy with activated LN cells draining different clones. In all 29 adoptive immunotherapy experiments, there was complete cross-reactivi ty between different MCA 106 tumor clones. These findings suggest that the MCA 106 tumor-specific antigen(s) that stimulates draining LN in vivo and recognized by the anti-CD3/IL-2 activated cells is present on most if not all tumor cells. However, in the absence of a demonstrabl y resistant tumor clone, a very highly polymorphic antigen with many c ross-reactive, but distinct epitopes might be operative and attributab le to these observations.