Strategy to augment the efficacy of immunotherapy for refractory breast cancer using trastuzumab combined adoptive cell therapy

Abstract

3062 Background: Antitumor monoclonal antibody (mAb) is able to make molecular change in cancer cells and may also induce immune response via its Fc domain. CTLs selectively kill autologous tumor cells (AuTCs) is powerful for adoptive cell therapy of cancer. To investigate the immunological activity and anti-cancer effect in the combination therapy using the anti-HER2 Mab (trastuzumab, Tr) with adoptive cell therapy, a pilot clinical trial was performed for patients (pts) with refractory breast cancer. Methods: Fourteen pts with recurrent breast cancer were enrolled, they all had failed the conventional chemoradiotherapy. MLTC was performed using PBMC and primary- cultured AuTCs for 7–14 days. The generated cells were analyzed by Flow Cytometry, and the cytokine production and killing activity were evaluated by the ELISA and 51Cr-release assay. The cells were administrated by intra-peritumoral injection biweekly and Tr (2mg/kg) was infused every week. The treatments were repeated for 6 to 22 injections, and the total numbers of administered T cells were reached to ∼5.6 x 109. To assess the mechanism of Tr-effects, the antigen-loaded dendritic cells (DC) were examined in the phenotype, cytokine productions, and the ability to induce HER2 specific T cells in vitro. Results: After ∼ 2 weeks of MLTC, the derived cells, containing a preponderance of CD3+CD4+ or CD8+ T cells and CD56+ NK cells, showed significant degrees of cytotoxicity and IFN-γ production against AuTCs and HLA-matched allogenic tumor cell lines in 4 cases tested. The clinical response showed PR/SD/PD was 1/6/7 and adverse effect was tolerable. The tumor marker proteins (CEA, etc) were decreased in 5 pts. The carcinomatous pleural effusion was well controlled in 6 pts. In DC experiments, Tr-opsonized antigen-loaded DC enhanced the ability to induce CD8+ T cells specific for HER2-peptides in IFN-γ ELISPOT assay. Conclusions: Clinical responses were observed in pts with refractory breast cancer after receiving the adoptive cell therapy plus Tr. Our results suggested that the efficacy of immunotherapy might be augmented by anti-Her2 mAb, and it might be in part due to the involvement of mAb in the ability of DC cross-presentation followed by the enhancement of antitumor cellular immunity. No significant financial relationships to disclose.