Specific adoptive immunotherapy mediated by tumor-draining lymph node cells sequentially activated with anti-CD3 and IL-2.

摘要: Lymph nodes (LN) draining progressively growing tumors contain tumor-sensitized but not fully functional preeffector lymphocytes. These cells could acquire therapeutic efficacy and be expanded upon sequential culture with anti-CD3 mAb for 2 days followed by incubation in IL-2 3 days. Using the weakly immunogenic MCA 106 205 murine sarcomas, we have further defined conditions of this anti-CD3/IL-2 activation which differentiated into immune effector cells. In vitro expansion required independent stimulation because simultaneous presence both at either stage did enhance activation. Generation two-stage was critically dependent on optimal concentrations (1.0 microgram/ml) (2-10 U/ml). However, these were inducing greatest cellular proliferation. adoptive immunotherapy experiments, although transfer anti-CD3/IL-2-activated alone mediate regression established metastases, concomitant administration enhanced vivo activity More importantly, tumor mediated found to immunologically specific. The specificity determined that stimulated cell response. spite their antitumor effects, tumor-draining LN exhibit detectable cytotoxicity against target 4-h 51Cr-release assay. mice bearing progressive tumor, contained most Some also detected spleen whereas mesenteric demonstrate any reactivity. kinetics studies, sensitization occurred between 4 6 after inoculation. As progressed, declined gradually suggesting a tumor-induced suppression. results define whereby stimulated, absence Ag, develop specific Our findings raise possibility using similar approaches isolating from cancer patients immunotherapy.