Effect of irradiation on cytokine production, MHC antigen expression, and vaccine potential of interleukin-2 and interferon-gamma gene-modified melanoma cells
Effect of irradiation on cytokine production, MHC antigen expression, and vaccine potential of interleukin-2 and interferon-gamma gene-modified melanoma cells
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DOI：
10.1006/cimm.1996.9991
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发表时间：
1996-08-01
影响因子：
4.3
通讯作者：
Seigler, HF
中科院分区：
文献类型：
--
作者：
AbdelWahab, Z;Dar, MM;Seigler, HF
最近的研究表明，转导有白细胞介素-2（IL-2）或干扰素-γ（IFN-γ）基因的肿瘤细胞在实验动物中刺激有效和特异的抗肿瘤免疫。为了用作人类疫苗，肿瘤细胞必须通过辐射灭活以确保其生长停滞。本研究旨在研究照射（10，000 rad）对IL-2和IFN-γ修饰的人黑色素瘤和B16小鼠黑色素瘤的生长特性和疫苗潜力的影响。辐射引起细胞生长停止和细胞数量逐渐减少。照射黑色素瘤细胞显示1.5至10倍增加的表面表达的MHC I类和/或II类抗原。MHC抗原的增加持续7-14天，然后下降。此外，IL-2和IFN-γ转导的黑色素瘤细胞表现出增强的细胞因子mRNA的表达和增加的细胞因子分泌后照射。在C57 BL/6小鼠中通过预防性免疫和免疫治疗以及在裸小鼠中通过混合移植试验来检查辐射对转导细胞的疫苗潜力的影响。经辐照的、经精氨酸转导的B16细胞疫苗与未经辐照的疫苗一样有效或更有效。这些辐照疫苗保护动物免受B16亲本细胞的致瘤剂量的挑战，并抑制4天建立的B16肺转移瘤的生长。经辐照的IL-α转导的人黑素瘤抑制受赞赏的亲本黑素瘤细胞生长的能力得以保留，但比未经辐照的细胞有效性低。结果表明，照射不会消除IL-2和IFN-γ转导的黑色素瘤的疫苗潜力。这些发现对利用细胞因子基因修饰的肿瘤细胞设计特异性主动免疫治疗方案具有意义。(C)出版社：Academic Press，Inc.
Recent studies have shown that tumor cells transduced with interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) genes stimulated a potent and specific antitumor immunity in experimental animals. For use as a human vaccine, tumor cells must be inactivated by irradiation to ensure the arrest of their growth. This study was undertaken to examine the effects of irradiation (10,000 rad) on the growth characteristics and vaccine potential of IL-2 and IFN-gamma-modified human melanomas and B16 murine melanoma. Irradiation caused cessation of cell growth and gradual reduction of cell number. Irradiated melanoma cells displayed 1.5 to 10-fold increases in the surface expression of MHC class I and/or class II antigens. The increases in MHC antigens persisted for 7-14 days postirradiation and then declined thereafter. Furthermore, IL-2- and IFN-gamma-transduced melanoma cells showed enhanced expression of the cytokine mRNA and increased cytokine secretion after irradiation. The effect of irradiation on the vaccine potential of the transduced cells was examined in C57BL/6 mice by prophylactic immunization and immunotherapy, and in nude mice by mixed transplantation assays. The irradiated, cytokine-transduced B16 cell vaccine was as or more effective than the unirradiated vaccine. These irradiated vaccines protected the animals against a challenging tumorigenic dose of B16 parental cells and suppressed the growth of 4-day-established B16 lung metastases. The ability of the irradiated IL-a-transduced human melanomas to inhibit the growth of admired parental melanoma cells was retained but was less efficacious than unirradiated cells. The results suggest that irradiation does not abrogate the vaccine potential of IL-2- and IFN-gamma-transduced melanomas. These findings have implications for designing specific active immunotherapy protocols utilizing cytokine gene-modified tumor cells. (C) 1996 Academic Press, Inc.