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.

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.

• Authors: Ji-Li Chen, Amina Dawoodji, Andrea Tarlton, Sacha Gnjatic, Abdelouahid Tajar, Ioannis Karydis, Judy Browning, Sarah Pratap, Christian Verfaille, Ralph R Venhaus, Linda Pan, Douglas G Altman, Jonathan S Cebon, Lloyd L Old, Paul Nathan, Christian Ottensmeier, Mark Middleton, Vincenzo Cerundolo
• Journal: International journal of cancer (Int J Cancer) Vol. 136 Issue 6 Pg. E590-601 (Mar 15 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25081390 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• CTAG1B protein, human
• Drug Combinations
• ISCOMATRIX
• Membrane Proteins
• Phospholipids
• Saponins
• Vaccines, Synthetic
• Cholesterol

Topics

• Adjuvants, Immunologic (pharmacology)
• Antibody Formation
• Antigens, Neoplasm (genetics, immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cholesterol (pharmacology)
• Drug Combinations
• Fowlpox virus (genetics)
• Humans
• Melanoma (immunology, therapy)
• Membrane Proteins (genetics, immunology)
• Phospholipids (pharmacology)
• Saponins (pharmacology)
• Vaccination
• Vaccines, Synthetic (immunology)