NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus

Chen, Ji-Li, Dawoodji, Amina, Tarlton, Andrea, Gnjatic, Sacha, Tajar, Abdelouahid, Karydis, Ioannis, Browning, Judy, Pratap, Sarah, Verfaille, Christian, Venhaus, Ralph R., Pan, Linda, Altman, Douglas G., Cebon, Jonathan S., Old, Lloyd L., Nathan, Paul, Ottensmeier, Christian, Middleton, Mark and Cerundolo, Vincenzo (2015) NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus. International Journal of Cancer, 136 (6), E590-E601. (doi:10.1002/ijc.29118). (PMID:25081390)

Abstract

Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8+ or CD4+ T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4+ T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8+ T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8+ T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179–102 and NY-ESO-1115–138 for CD4+ T cells and NY-ESO-185–108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.

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