Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes:: Clinical and immunologic findings
Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes:: Clinical and immunologic findings
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DOI：
10.1200/jco.2002.09.134
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发表时间：
2002-10-15
影响因子：
45.3
通讯作者：
Parmiani, G
中科院分区：
文献类型：
--
作者：
Belli, F;Testori, A;Parmiani, G
目的：确定由自体肿瘤源性热休克蛋白gp 96-肽复合物组成的疫苗的免疫原性和抗肿瘤活性（HSPPC-96，Oncophage; Antigenics，Inc，Woburn，M）（美国癌症联合委员会IV期）黑色素瘤患者。患者和方法：64名患者接受了疫苗生产所需的转移组织手术切除，42名患者能够接受疫苗，39例在一个接种周期（每周注射4次）后可评估。21名患者因没有出现进展而接受了第二个周期（每两周注射四次）。通过酶联免疫斑点（ELISPOT）试验对接种前后获得的外周血单核细胞（PBMC）进行抗原特异性抗黑色素瘤T细胞应答评估。肿瘤组织的免疫组化分析也performed.Results：没有观察到治疗相关的毒性。在28例可测量疾病的患者中，2例在随访结束时完全缓解（CR），3例疾病稳定（SD）。CR持续时间分别为559+和703+天，而SD分别持续153、191和272天。23名受试者的PBMC的ELISPOT试验显示，11名患者的接种后黑素瘤特异性T细胞斑点数量显著增加，临床应答者显示T细胞活性增加的频率很高。免疫组化染色的黑色素瘤组织从疫苗的生产揭示了高表达的HLA I类和黑色素瘤抗原在7个8个临床应答者（2个CR，3个SD，3个长期无病生存），并在4个12 nonrespons.Conclusion：自体HSPPC-96的转移性黑色素瘤患者的疫苗是可行的，没有显着的毒性。该疫苗在少数患者中诱导了临床和肿瘤特异性T细胞应答。
Purpose : To determine the immunogenicity and antitumor activity of a vaccine consisting of autologous, tumor-derived heat shock protein gp96-peptide complexes (HSPPC-96, Oncophage; Antigenics, Inc, Woburn, M) in metastatic (American Joint Committee on Cancer stage IV) melanoma patients.Patients and Methods: Sixty-four patients had surgical resection of metastatic tissue required for vaccine production, 42 patients were able to receive the vaccine, and 39 were assessable after one cycle of vaccination (four weekly injections). In 21 patients, a second cycle (four biweekly injections) was given because no progression occurred. Antigen-specific antimelanoma T-cell response was assessed by enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Immunohistochemical analyses of tumor tissues were also performed.Results: No treatment-related toxicity was observed. Of 28 patients with measurable disease, two had a complete response (CR) and three had stable disease (SD) at the end of follow-up. Duration of CR was 559+ and 703+ days, whereas SD lasted for 153, 191, and 272 days, respectively. ELISPOT assay with PBMCs of 23 subjects showed a significantly increased number of postvaccination melanoma-specific T-cell spots in 11 patients, with clinical responders displaying a high frequency of increased T-cell activity. Immunohistochemical staining of melanoma tissues from which vaccine was produced revealed high expression of both HLA class I and melanoma antigens in seven of eight clinical responders (two with CR, three with SD, and the three with long-term disease-free survival) and in four of 12 nonresponders.Conclusion: Vaccination of metastatic melanoma patients with autologous HSPPC-96 is feasible and devoid of significant toxicity. This vaccine induced clinical and tumor-specific T-cell responses in a significant minority of patients.