Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients.
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.
Jäger
Elke
E
Ludwig Institute Clinical Trial Center, Medizinische Klinik II, Hämatologie-Onkologie, Krankenhaus Nordwest, Steinbacher Hohl 2-26, 60488 Frankfurt, Germany. elke.jaeger@licr.org
Karbach
Julia
J
Gnjatic
Sacha
S
Neumann
Antje
A
Bender
Armin
A
Valmori
Danila
D
Ayyoub
Maha
M
Ritter
Erika
E
Ritter
Gerd
G
Jäger
Dirk
D
Panicali
Dennis
D
Hoffman
Eric
E
Pan
Linda
L
Oettgen
Herbert
H
Old
Lloyd J
LJ
Knuth
Alexander
A
D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005587:Fowlpox virus / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D000906:Antibodies; D019496:Cancer Vaccines; D000939:Epitopes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; C504237:peptide NY-ESO-1 157-165