Recombinant Vaccinia/Fowlpox NY-ESO-1 Vaccines Induce Both Humoral and Cellular NY-ESO-1-Specific Immune Responses in Cancer Patients

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-09, Vol.103 (39), p.14453-14458
• Main Authors: Jäger, Elke, Karbach, Julia, Gnjatic, Sacha, Neumann, Antje, Bender, Armin, Valmori, Danila, Ayyoub, Maha, Ritter, Erika, Ritter, Gerd, Jäger, Dirk, Panicali, Dennis, Hoffman, Eric, Pan, Linda, Oettgen, Herbert, Old, Lloyd J., Knuth, Alexander
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies - blood; Antibody Formation - immunology; Antigens; Biological Sciences; Cancer; Cancer Vaccines - adverse effects; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; Cells; Clone Cells; Cohort Studies; Cytotoxicity, Immunologic - immunology; Epitopes; Epitopes - immunology; Fowlpox virus - metabolism; Humans; Immune response; Immune system; Immunity, Cellular - immunology; Melanoma; Membrane Proteins - immunology; Neoplasm Proteins - immunology; Neoplasms - immunology; Peptide Fragments - immunology; Reactivity; T lymphocytes; Tumors; Vaccination; Vaccines; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccinia virus - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0606512103

NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and/or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.