Doré J F, Portoukalian J, Berthier-Vergnes O, Jacubovich R, Genève J, Bailly M, Lefthériotis E, Weissbrod A, Mayer M
INSERM U218, Centre Léon-Bérard, Lyon, France.
Bull Cancer. 1990;77(9):881-91.
Thirty-two patients with high risk melanoma (either primary melanoma of the limbs or trunk, or recurrent melanoma) and clinically disease-free following appropriate surgical treatment were immunized with a vaccinia virus oncolysate made from a pool of 4 human melanoma cell lines. Injections were given id weekly for 3 months, and then bi-monthly for a further 21 months or until relapse. Treated patients have been under study for 11-72 months, and 15 of them for more than 36 months. Twelve patients received a full 24-month treatment: 3 relapsed and 10 are alive (9 of them disease-free) with a survival of 34-72 months. One patient is still under treatment. Nineteen patients relapsed during treatment: among the 13 patients that relapsed early during the course of treatment, 9 patients died after a survival of 5-30 months and 4 are alive with a survival of 30-59 months; among the 6 patients that later relapsed, 2 patients died after a survival of 21 and 29 months and 4 are alive with a survival of 16-69 months. An analysis of the patients' disease-free survival and overall survival was made using the actuarial method, and limited to 5 years: the disease-free survival curve shows a 35% plateau reached after 40 months, and the survival curve shows a 60% plateau reached after 30 months. The patients' responses to the immunization antigens expressed by the oncolysate were studied. Lymphocytes from immunized patients do respond in vitro to the stimulation by oncolysate in the presence of low amounts of IL-2, and this response is greater than that of normal individuals. IgG antibody production to gangliosides with N-glycolyl neuraminic acid is of prognostic significance, the increase in IgG anti-ganglioside antibody in patients after 3 and 6 months of treatment being linked to the absence of relapse in these patients. Finally, preliminary results show, in several patients under treatment, the appearance of antibodies directed against a 31 kD protein of the oncolysate not detectable in the vaccinia virus or in melanoma cell lysates. Such results are in accordance with previously reported ones from similar studies conducted by other investigators and tend to indicate the efficacy of vaccinia virus oncolysate immunization in the treatment of high risk melanoma.
32例高危黑色素瘤患者（包括四肢或躯干原发性黑色素瘤或复发性黑色素瘤），经适当手术治疗后临床无病，用由4种人黑色素瘤细胞系混合制成的痘苗病毒溶瘤产物进行免疫。每周一次皮内注射，共3个月，然后每两个月一次，持续21个月或直至复发。接受治疗的患者已随访11 - 72个月，其中15例随访超过36个月。12例患者接受了完整的24个月治疗：3例复发，10例存活（其中9例无病），生存期为34 - 72个月。1例患者仍在治疗中。19例患者在治疗期间复发：在治疗早期复发的13例患者中，9例在存活5 - 30个月后死亡，4例存活，生存期为30 - 59个月；在后期复发的6例患者中，2例在存活21个月和29个月后死亡，4例存活，生存期为16 - 69个月。采用精算方法对患者的无病生存期和总生存期进行分析，且限于5年：无病生存曲线显示40个月后达到35%的平台期，生存曲线显示30个月后达到60%的平台期。研究了患者对溶瘤产物表达的免疫抗原的反应。免疫患者的淋巴细胞在低剂量IL - 2存在下，体外确实对溶瘤产物的刺激有反应，且这种反应大于正常个体。对含N - 羟乙酰神经氨酸神经节苷脂的IgG抗体产生具有预后意义，治疗3个月和6个月后患者体内IgG抗神经节苷脂抗体的增加与这些患者无复发相关。最后，初步结果显示，在数例接受治疗的患者中，出现了针对溶瘤产物中一种31 kD蛋白的抗体，在痘苗病毒或黑色素瘤细胞裂解物中未检测到。这些结果与其他研究者先前进行的类似研究报告一致，倾向于表明痘苗病毒溶瘤产物免疫治疗高危黑色素瘤的有效性。
