Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade
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...
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| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/8121985 |
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| author | Michal Lotem Sharon Merims Stephen Frank Tamar Hamburger Aviram Nissan Luna Kadouri Jonathan Cohen Ravid Straussman Galit Eisenberg Shoshana Frankenburg Einat Carmon Bilal Alaiyan Shlomo Shneibaum Zeynep Ozge Ayyildiz Murat Isbilen Kerem Mert Senses Ilan Ron Hanna Steinberg Yoav Smith Eitan Shiloni Ali Osmay Gure Tamar Peretz |
| author_facet | Michal Lotem Sharon Merims Stephen Frank Tamar Hamburger Aviram Nissan Luna Kadouri Jonathan Cohen Ravid Straussman Galit Eisenberg Shoshana Frankenburg Einat Carmon Bilal Alaiyan Shlomo Shneibaum Zeynep Ozge Ayyildiz Murat Isbilen Kerem Mert Senses Ilan Ron Hanna Steinberg Yoav Smith Eitan Shiloni Ali Osmay Gure Tamar Peretz |
| author_sort | Michal Lotem |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b0c0d51f759f48f1ab4d16a4278f5084 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-b0c0d51f759f48f1ab4d16a4278f50842025-02-03T06:01:32ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/81219858121985Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 BlockadeMichal Lotem0Sharon Merims1Stephen Frank2Tamar Hamburger3Aviram Nissan4Luna Kadouri5Jonathan Cohen6Ravid Straussman7Galit Eisenberg8Shoshana Frankenburg9Einat Carmon10Bilal Alaiyan11Shlomo Shneibaum12Zeynep Ozge Ayyildiz13Murat Isbilen14Kerem Mert Senses15Ilan Ron16Hanna Steinberg17Yoav Smith18Eitan Shiloni19Ali Osmay Gure20Tamar Peretz21Sharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelDepartments of Surgery, Hadassah Hebrew University Hospital, Mount Scopus Campus, 91240 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelDepartment of Molecular Cell Biology, Weizmann Institute of Science, 7610001 Rehovot, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelDepartments of Surgery, Hadassah Hebrew University Hospital, Mount Scopus Campus, 91240 Jerusalem, IsraelDepartments of Surgery, Hadassah Hebrew University Hospital, Mount Scopus Campus, 91240 Jerusalem, IsraelDepartment of Surgery, Tel Aviv Sourasky Medical Center, 64239 Tel Aviv, IsraelDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, TurkeyDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, TurkeyDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, TurkeyDepartment of Oncology, Tel Aviv Sourasky Medical Center, 64239 Tel Aviv, IsraelSharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelGenomic Data Analysis Unit, Hebrew University Medical School, 91120 Jerusalem, IsraelDepartment of Surgery, Bnai Zion Medical Center, 31048 Haifa, IsraelDepartment of Molecular Biology and Genetics, Bilkent University, 06800 Ankara, TurkeySharett Institute of Oncology, Hadassah Hebrew University Hospital, Ein Karem Campus, 91120 Jerusalem, IsraelBackground. 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.http://dx.doi.org/10.1155/2016/8121985 |
| spellingShingle | Michal Lotem Sharon Merims Stephen Frank Tamar Hamburger Aviram Nissan Luna Kadouri Jonathan Cohen Ravid Straussman Galit Eisenberg Shoshana Frankenburg Einat Carmon Bilal Alaiyan Shlomo Shneibaum Zeynep Ozge Ayyildiz Murat Isbilen Kerem Mert Senses Ilan Ron Hanna Steinberg Yoav Smith Eitan Shiloni Ali Osmay Gure Tamar Peretz Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade Journal of Immunology Research |
| title | Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade |
| title_full | Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade |
| title_fullStr | Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade |
| title_full_unstemmed | Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade |
| title_short | Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade |
| title_sort | adjuvant autologous melanoma vaccine for macroscopic stage iii disease survival biomarkers and improved response to ctla 4 blockade |
| url | http://dx.doi.org/10.1155/2016/8121985 |
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