Purpose: Recent accumulating data indicate that therapeutic efficacy of anti-tumor antibodies might be in part attributed to the ADCC activity and induction of tumor specific T cell immunity mediated by FcR on dendritic cells. Immune dysfunction might be a limited factor in antiboby therapy with advanced cancer patients. Based on these knowledge, a clinical trial was performed to test therapeutic efficacy of Trastuzumab combined with immunotherapy in patients with HER2+ breast cancer. Method: 14 pts with recurrent breast cancer (7 HER2+; 7 HER2-), who had failed the conventional chemoradiotherapy., were enrolled in this study. The tumor cell suspensions were prepared by mincing and enzymatic digestion of the biopsied fresh tumors. AuTL was generated in vitro by co-culture of peripheral blood lymphocytes (PBL) and irradiated autologous tumor cells in RPMI 1640 medium supplemented with rIL-2 (100 u/ml) for 7-14 days. The surface markers of the generated AuTLs and cytokine productions were analyzed by Flow Cytometry and ELISA, respectively. The killing activity and IFN-g production against autologous tumor cells were also evaluated in presence or absence of Trastuzumab (100 ug/ml). These AuTLs were administrated in the patients by intra-peritumoral injection biweekly, and Trastuzumab (2mg/kg) was systemically infused for the HER2+ patients weekly. The treatments were repeated for 6 to 11 cycles, in which total numbers of administered T cells ranged between 3.2 x 109 and 4.6 x 109. Results: The generated AuTLs were preponderantly CD3+CD4+ / CD3+ CD8+ T cells and CD3-CD56+ NK cells and showed significant degrees of cytotoxic activity and IFN-g production against autologous tumor cells and also HLA matched allogenic tumor cell lines in 4 out of 6 cases tested. ADCC was enhanced in 4 cases. The clinical response showed the one PR and seven NCs in these 14 pts. It is noted that carcinomatous pleural effusion was disappeared or well controlled in 6 pts and tumor marker proteins (CEA, CA15-3, TPA)were markedly decreased in 5 pts. The adverse effects of the immunotherapy were tolerable with grade 1∼2 infusion reaction of fever, nausea and fatigue, and no cardiac dysfunction was observed. CONCLUSIONS: Clinical responses with the intra-peritumoral AuTL injection were observed in patients with refractory recurrent breast cancer. These preliminary data suggest that the strategy of the combination therapy may benefit heavily refractory recurrence breast cancer patients.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]