Adjuvant autologous melanoma vaccine for macroscopic stage III disease: survival, biomarkers, and improved response to CTLA-4 blockade
Journal of Immunology Research
8121985-1 - 8121985-12
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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.
Autologous melanoma vaccine
B Raf kinase
Cancer testis antigen
Cytotoxic T lymphocyte antigen 4
Cytotoxic T lymphocyte antigen 4
Disease free survival
Injection site erythema
Major clinical study
Phase 2 clinical trial
Antagonists and inhibitors
Kaplan Meier method
Molecularly targeted therapy
Multimodality cancer therapy
Tumor cell line
Aged, 80 and over
Combined Modality Therapy
Gene Expression Profiling
Published Version (Please cite this version)https://doi.org/10.1155/2016/8121985
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