Bystryn J C
Ronald O. Perelman Department of Dermatology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, NY 10016, USA.
Recent Results Cancer Res. 1995;139:337-48. doi: 10.1007/978-3-642-78771-3_26.
We have developed a partially purified, polyvalent melanoma vaccine from surface material shed into culture medium by a pool of selected melanoma cells. The vaccine contains a broad spectrum of melanoma antigens to circumvent the antigenic heterogeneity of melanoma and to obviate the need to identify individual antigens that mediate tumor-protective immunity. Vaccine treatment augments antimelanoma humoral and/or cellular immunity in over 50% of patients and can increase immunity to a patient's own melanoma. Vaccine-induced antibodies are directed at one or more surface antigens with molecular masses of 210, 150, 110, 75, or 38 kDa. The 210- and 110-kDa antigens are melanoma associated, as they were expressed by four of five human melanoma cell lines, but by only two of 12 control cell lines, and are unrelated to previously described melanoma antigens. The disease-free (DF) and overall survival (OS) of vaccine-treated patients with surgically resected stage II (regional) disease is 50% longer than that of historical controls. Survival is particularly prolonged in patients who develop an immune response. Median DF survival is 4.7 years longer and OS 3.7 years longer in patients with a strong, as opposed to no, cellular immune response to vaccine treatment (p = < 0.02). Similarly, median DF survival of patients with vaccine-induced melanoma antibodies is significantly longer than that of nonresponders (65 months vs. 17 months, respectively), as is overall survival (p = 0.01). These differences in outcome are unrelated to disease severity or to the overall immunological competence of the patients, suggesting they result from vaccine treatment. Thus melanoma vaccine treatment is safe, capable of stimulating antimelanoma immunity in many patients, and appears to be clinically effective in delaying the progression of this cancer in some individuals.
我们从一组选定的黑色素瘤细胞分泌到培养基中的表面物质中，研制出了一种部分纯化的多价黑色素瘤疫苗。该疫苗包含多种黑色素瘤抗原，以克服黑色素瘤的抗原异质性，避免识别介导肿瘤保护性免疫的单个抗原的必要性。疫苗治疗可增强超过50%患者的抗黑色素瘤体液和/或细胞免疫，并能增强患者对自身黑色素瘤的免疫力。疫苗诱导产生的抗体针对一种或多种分子量为210、150、110、75或38 kDa的表面抗原。210 kDa和110 kDa的抗原与黑色素瘤相关，因为它们在五个人类黑色素瘤细胞系中的四个中表达，但在12个对照细胞系中只有两个表达，且与先前描述的黑色素瘤抗原无关。接受手术切除的II期（局部）疾病的疫苗治疗患者的无病生存期（DF）和总生存期（OS）比历史对照长50%。在产生免疫反应的患者中，生存期尤其延长。与对疫苗治疗无细胞免疫反应的患者相比，对疫苗治疗有强烈细胞免疫反应的患者的中位DF生存期长4.7年，OS长3.7年（p = < 0.02）。同样，产生疫苗诱导的黑色素瘤抗体的患者的中位DF生存期明显长于无反应者（分别为65个月和17个月），总生存期也是如此（p = 0.01）。这些结果差异与疾病严重程度或患者的整体免疫能力无关，表明它们是由疫苗治疗引起的。因此，黑色素瘤疫苗治疗是安全的，能够在许多患者中刺激抗黑色素瘤免疫，并且在一些个体中似乎在临床上有效地延缓了这种癌症的进展。
