Arienti F, Belli F, Napolitano F, Sulé-Suso J, Mazzocchi A, Gallino G F, Cattelan A, Santantonio C, Rivoltini L, Melani C, Colombo M P, Cascinelli N, Maio M, Parmiani G
Division of Experimental Oncology D, Instituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Hum Gene Ther. 1999 Dec 10;10(18):2907-16. doi: 10.1089/10430349950016320.
A human melanoma line genetically modified to release interleukin 4 (IL-4) was utilized to immunize advanced melanoma patients in order to elicit or increase a specific anti-melanoma immune response, which may affect distant lesions. Twelve metastatic melanoma patients were injected subcutaneously at least three times with 5 x 10(7) IL-4 gene-transduced and irradiated allogeneic melanoma cells per dose. Both systemic and local toxicities were mild, consisting of transient fever and erythema, swelling, and induration at the vaccination site. Two mixed but not complete or partial clinical responses were recorded. To assess the immune response of vaccinated patients, both serological and cell-mediated activities were evaluated. Antibodies to alloantigens could be detected in 2 of 11 patients tested. Mixed tumor-lymphocyte cultures were performed, utilizing autologous and allogeneic HLA-A2-matched melanoma lines as simulators and targets. A significant increase in IFN-gamma release was detected in 7 of 11 cases when postvaccination lymphocytes were stimulated by the untransduced allomelanoma cells. However, induction of a specific recognition of autologous melanoma cells by PBLs was obtained after vaccination in only one of six cases studied. This response involved the melanoma peptide Melan-A/MART-1(27-35) that was recognized in an HLA-A2-restricted fashion. These results indicate that vaccination with allogeneic melanoma cells releasing IL-4 locally can expand a T cell response against antigen(s) of autologous, untransduced tumor, although in a minority of patients.
利用一种经过基因改造可释放白细胞介素4（IL-4）的人黑色素瘤细胞系对晚期黑色素瘤患者进行免疫，以引发或增强特异性抗黑色素瘤免疫反应，这可能会影响远处病灶。12例转移性黑色素瘤患者每剂皮下注射至少3次，每次注射5×10⁷个经IL-4基因转导并照射的同种异体黑色素瘤细胞。全身和局部毒性均较轻，包括短暂发热以及接种部位的红斑、肿胀和硬结。记录到2例混合但非完全或部分的临床反应。为评估接种患者的免疫反应，对血清学和细胞介导活性均进行了评估。在11例接受检测的患者中，有2例检测到针对同种异体抗原的抗体。利用自体和与HLA-A2匹配的同种异体黑色素瘤细胞系作为刺激物和靶标进行混合肿瘤淋巴细胞培养。当接种后淋巴细胞受到未转导的同种黑色素瘤细胞刺激时，在11例中有7例检测到IFN-γ释放显著增加。然而，在研究的6例中，仅1例在接种后获得了外周血淋巴细胞（PBLs）对自体黑色素瘤细胞的特异性识别。这种反应涉及以HLA-A2限制方式被识别的黑色素瘤肽Melan-A/MART-1(27 - 35)。这些结果表明，局部释放IL-4的同种异体黑色素瘤细胞接种可使针对自体未转导肿瘤抗原的T细胞反应扩大，尽管仅在少数患者中出现这种情况。
