Recombinant vaccinia/fowipox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

被引:174
作者
Jaeger, Elke
Karbach, Julia
Gnjatic, Sacha
Neumann, Antje
Bender, Armin
Valmori, Danila
Ayyoub, Maha
Ritter, Erika
Ritter, Gerd
Jaeger, Dirk
Panicali, Dennis
Hoffman, Eric
Pan, Linda
Oettgen, Herbert
Old, Lloyd J.
Knuth, Alexander
机构
[1] Krankenhaus Nordw, Med Klin 2, Ludwig Inst Clin Trial Ctr, D-60488 Frankfurt, Germany
[2] Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY 10021 USA
[3] Columbia Univ Coll Phys & Surg, Ludwig Inst Clin Trial Ctr, New York, NY 10032 USA
[4] Univ Heidelberg, Nationales Centrum Tumorerkrankungen, D-69120 Heidelberg, Germany
[5] Ther Biol Corp, Cambridge, MA 02142 USA
[6] Univ Spital Zurich, Klin & Poliklin Onkol, CH-8091 Zurich, Switzerland
关键词
antibody response; NY-ESO-1 recombinant vaccine; T cell response; tumor reactivity;
D O I
10.1073/pnas.0606512103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
NY-ESO-1 is a cancer/testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-11 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 INY-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.
引用
收藏
页码:14453 / 14458
页数:6
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