Cancer immunotherapy with peptide-based vaccines: What have we achieved? - Where are we going?

被引:324
作者
Parmiani, G
Castelli, C
Dalerba, P
Mortarini, R
Rivoltini, L
Marincola, FM
Anichini, A
机构
[1] Ist Nazl Studio & Cura Tumori, Unit Immunotherapy Human Tumors, I-20133 Milan, Italy
[2] Ist Nazl Studio & Cura Tumori, Unit Immunobiol Human Tumors, I-20133 Milan, Italy
[3] NIH, Immunogenet Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA
来源
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2002年 / 94卷 / 11期
关键词
D O I
10.1093/jnci/94.11.805
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Many human tumor-associated antigens (TAAs) have recently been identified and molecularly characterized. When bound to major histocompatibility complex molecules, TAA peptides are recognized by, T cells. Clinical studies have therefore been initiated to assess the therapeutic potential of active immunization or vaccination with TAA peptides in patients with metastatic cancer. So far, only a limited number of TAA peptides, mostly those recognized by CD8(+) T cells in melanoma patients, have been clinically tested. In some clinical trials, partial or complete tumor regression was observed in approximately 10%-30% of patients. No serious side effects have been reported. The clinical responses, however, were often not associated with a detectable T-cell-specific antitumor immune response when patients' T cells were evaluated in ex vivo assays. In this review, we analyze the available human TAA peptides, the potential immunogenicity (i.e., the ability to trigger a tumor-specific T-cell response) of TAA peptides in vitro and ex vivo, and the potential to construct slightly modified forms of TAA peptides that have increased T-cell stimulatory activity. We discuss the available data from clinical trials of TAA peptide-based vaccination (including those that used dendritic cells to present TAA peptides), identify possible reasons for the limited clinical efficacy of these vaccines, and suggest ways to improve the clinical outcome of TAA peptide-based vaccination for cancer patients.
引用
收藏
页码:805 / 818
页数:14
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