Purpose: Previous studies have shown that chemotherapy given prior to vaccine can inhibit vaccine mediated antitumor immunity. Since chemotherapy is standard of care for many cancer types, the possibility that chemotherapy can be used concomitantly with vaccine was evaluated. We hypothesized that one could take advantage of the fact that certain chemotherapy regimens induce transient pancytopenia, which is followed by a recovery phase. We examined if administering vaccine during the T-cell recovery phase would enhance the effectiveness of the vaccine. Moreover, we examined the effects of chemotherapy on the quantity and function of regulatory T-cells. Many non-small cell lung cancer (NSCLC) patients undergo surgery followed by standard-of-care adjuvant chemotherapy, which includes cisplatin in combination with vinorelbine. In spite of therapy, the median survival of patients with metastatic disease is less than 10 months. Experimental Design: We evaluated the potential for biological synergism between the standard-of-care chemotherapy regimen and a recombinant yeast-CEA vaccine in a mouse model of NSCLC. We also examined the translational potential of our preclinical findings by evaluating the effect of chemotherapy on CTL-mediated cytolysis of human NSCLC tumor cell lines in vitro. Results: These studies demonstrate for the first time that (a) the combination of cisplatin plus vinorelbine modulates CD4+, CD8+, CD19+, natural killer, and regulatory T-cell populations in healthy mice; and (b) cisplatin plus vinorelbine combined with heat-killed recombinant yeast-CEA vaccine (i) is superior to either modality alone at reducing tumor burden and (ii) increases vaccine mediated antigen-specific T-cell responses. Moreover, cisplatin plus vinorelbine modulates the cell surface expression of immunologically relevant molecules and improves antigen-specific CTL mediate cytotoxicity in vitro. Conclusions: These finding suggest potential clinical benefit for the combined use of recombinant yeast vaccine and cisplatin-based chemotherapy regimens.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 363.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009