TY - JOUR
T1 - Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease
T2 - Survival, Biomarkers, and Improved Response to CTLA-4 Blockade
AU - Lotem, Michal
AU - Merims, Sharon
AU - Frank, Stephen
AU - Hamburger, Tamar
AU - Nissan, Aviram
AU - Kadouri, Luna
AU - Cohen, Jonathan
AU - Straussman, Ravid
AU - Eisenberg, Galit
AU - Frankenburg, Shoshana
AU - Carmon, Einat
AU - Alaiyan, Bilal
AU - Shneibaum, Shlomo
AU - Ayyildiz, Zeynep Ozge
AU - Isbilen, Murat
AU - Senses, Kerem Mert
AU - Ron, Ilan
AU - Steinberg, Hanna
AU - Smith, Yoav
AU - Shiloni, Eitan
AU - Gure, Ali Osmay
AU - Peretz, Tamar
N1 - Publisher Copyright:
© 2016 Michal Lotem et al.
PY - 2016
Y1 - 2016
N2 - Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.
AB - Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.
UR - http://www.scopus.com/inward/record.url?scp=84973131338&partnerID=8YFLogxK
U2 - 10.1155/2016/8121985
DO - 10.1155/2016/8121985
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AN - SCOPUS:84973131338
SN - 2314-8861
VL - 2016
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 8121985
ER -
