IMPROVED SURVIVAL WITH ADJUVANT IMMUNOTHERAPY AFTER SURGICAL RESECTION IN A MURINE MODEL

Background: Adoptive immunotherapy has met with limited success in the treatment of bulky metastatic disease. The purpose of this study was to determine whether lymphocytes stimulated in vitro could improve sur vival when given as an adjuvant to surgical resection in animals harbo ring microscopic metastatic disease. Methods: Lymphocytes from nodes d raining the primary tumor (DLN lymphocytes) were stimulated in vitro w ith phorbol 12,13-dibutyrate and ionomycin and used as adjuvant immuno therapy after surgical resection of the primary tumor. Mice with advan ced P-815 footpad tumors and disseminated microscopic metastases under went amputation of the tumor-bearing extremity and were randomized to various adjuvant treatments. Results: Mice treated with adjuvant immun otherapy using stimulated DLN lymphocytes demonstrated significantly i mproved survival, showing that DLN lymphocytes stimulated in vitro can abrogate metastases that are invading multiple organs simultaneously. Mice successfully treated with adjuvant immunotherapy demonstrated lo ng-term (80 days) in vivo antitumor activity by rejecting subsequent t umor challenge. In addition, stimulated DLN lymphocytes provided in vi vo antitumor activity to naive mice. Conclusions: Adjuvant immunothera py after resection in the face of residual microscopic tumor burden ma y prove to be a useful application of adoptive immunotherapy.