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Yayınlanmış 1 Ocak 2016 | Sürüm v1
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Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

Oluşturanlar

  • 1. Hadassah Hebrew Univ Hosp, Sharett Inst Oncol, Karem Campus, IL-91120 Jerusalem, Israel
  • 2. Hadassah Hebrew Univ Hosp, Dept Surg, Mt Scopus Campus, IL-91240 Jerusalem, Israel
  • 3. Weizmann Inst Sci, Dept Mol Cell Biol, IL-7610001 Rehovot, Israel
  • 4. Tel Aviv Sourasky Med Ctr, Dept Surg, IL-64239 Tel Aviv, Israel
  • 5. Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey
  • 6. Tel Aviv Sourasky Med Ctr, Dept Oncol, IL-64239 Tel Aviv, Israel
  • 7. Hebrew Univ Jerusalem, Genom Data Anal Unit, Sch Med, IL-91120 Jerusalem, Israel
  • 8. Bnai Zion Med Ctr, Dept Surg, IL-31048 Haifa, Israel

Açıklama

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.

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