Kominsky S L, Torres B A, Hobeika A C, Lake F A, Johnson H M
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Int J Cancer. 2001 Dec 15;94(6):834-41. doi: 10.1002/ijc.1551.
B16F10 melanoma is a tumor derived from C57BL/6 mice that has been found to be poorly immunogenic and highly aggressive. Here we have shown that vaccination of mice with irradiated B16F10 cells followed by treatment with a combination of staphylococcal enterotoxins A and B (SEA/SEB) leads to significant and specific protection against subsequent challenge with viable B16F10 cells (at least 25-fold greater than a lethal dose). Also, 75% of mice surviving over 150 days remained tumor-free after rechallenge with viable B16F10 cells, evidence of the development of strong immunologic memory. Additional studies showed increases in CD4(+) and CD8(+) T-cell populations, cytotoxic T-lymphocyte activity and interferon-gamma production, all of which may contribute to enhanced survival. Furthermore, failure to produce protection in either CD4(-/-) or CD8(-/-) T-cell knockout mice is evidence that CD4(+) and CD8(+) T cells play an essential role in induction of immunity. These results show that superantigen administration subsequent to vaccination with inactivated tumor cells results in protective antitumor immunity. Thus, prophylactic vaccination against cancer is a feasible method for arming the immune system prior to the incidence of cancer.
B16F10黑色素瘤是一种源自C57BL/6小鼠的肿瘤，已发现其免疫原性较差且侵袭性很强。我们在此表明，用经辐照的B16F10细胞对小鼠进行疫苗接种，随后用葡萄球菌肠毒素A和B（SEA/SEB）联合治疗，可对随后用活的B16F10细胞进行的攻击产生显著且特异性的保护作用（比致死剂量大至少25倍）。此外，存活超过150天的小鼠中有75%在用活的B16F10细胞再次攻击后仍无肿瘤，这是强大免疫记忆形成的证据。进一步的研究表明，CD4(+)和CD8(+) T细胞群体增加、细胞毒性T淋巴细胞活性增强以及干扰素-γ产生增加，所有这些都可能有助于提高存活率。此外，在CD4(-/-)或CD8(-/-) T细胞敲除小鼠中未能产生保护作用，证明CD4(+)和CD8(+) T细胞在免疫诱导中起关键作用。这些结果表明，在用灭活肿瘤细胞进行疫苗接种后给予超抗原可产生保护性抗肿瘤免疫。因此，癌症预防性疫苗接种是在癌症发生之前增强免疫系统的一种可行方法。
