Immunologic and clinical outcomes of a Randomized phase II trial of two multipeptide Vaccines for melanoma in the adjuvant setting
Immunologic and clinical outcomes of a Randomized phase II trial of two multipeptide Vaccines for melanoma in the adjuvant setting
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DOI：
10.1158/1078-0432.ccr-07-0486
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发表时间：
2007-11-01
影响因子：
11.5
通讯作者：
Rehm, Patrice K.
中科院分区：
文献类型：
--
作者：
Slingluff, Craig L., Jr.;Petroni, Gina R.;Rehm, Patrice K.
目的：人黑色素瘤细胞表达由CD 8（+）T淋巴细胞识别的共有抗原，其中最常见的是黑色素细胞分化蛋白和癌症睾丸抗原。然而，用于黑素瘤的肽疫苗通常仅靶向一种或两种MHC I类相关的肽抗原。由于黑色素瘤通常通过选择性抗原丢失来逃避免疫识别，因此黑色素瘤疫苗的优化可能需要开发更复杂的多肽疫苗。在一项前瞻性随机临床试验中，我们评估了一种疫苗的安全性和免疫原性，该疫苗含有来自黑素细胞分化蛋白和癌症睾丸抗原的12种肽的混合物，设计用于代表80%黑素瘤患者群体的人类白细胞抗原类型。将其与仅具有黑素细胞分化肽的四肽疫苗进行比较。结果：这些数据表明：（a）12肽混合物在所有治疗的患者中是免疫原性的;（B）尽管与另外的肽竞争结合MHC分子，但单个肽的免疫原性得以维持;（c）用更复杂的12肽混合物接种诱导更广泛和更强的免疫应答;和（d）在这个肽疫苗试验的临床结果与外周血lymphocyte.Conclusions中测量的免疫应答相关：这些数据支持继续研究复杂的多肽疫苗用于黑色素瘤。
Purpose: Human melanoma cells express shared antigens recognized by CD8(+) T lymphocytes, the most common of which are melanocytic differentiation proteins and cancer-testis antigens. However, peptide vaccines for melanoma usually target only one or two MHC class I-associated pepticle antigens. Because melanomas commonly evade immune recognition by selective antigen loss, optimization of melanoma vaccines may require development of more complex multipepticle vaccines.Experimental Design: In a prospective randomized clinical trial, we have evaluated the safety and immunogenicity of a vaccine containing a mixture of 12 peptides from melanocytic differentiation proteins and cancer-testis antigens, designed for human leukocyte antigen types that represent 80% of the melanoma patient population. This was compared with a four-peptide vaccine with only melanocytic differentiation peptides. Immune responses were assessed in peripheral blood and in vaccine-draining lymph nodes.Results: These data show that (a) the 12-peptide mixture is immunogenic in all treated patients; (b) immunogenicity of individual peptides is maintained despite competition with additional peptides for binding to MHC molecules; (c) a broader and more robust immune response is induced by vaccination with the more complex 12-peptide mixture; and (d) clinical outcome in this peptide vaccine trial correlates with immune responses measured in the peripheral blood lymphocytes.Conclusions: These data support continued investigation of complex multipeptide vaccines for melanoma.