Böhm W, Schirmbeck R, Reimann J
Department of Medical and Microbiological Hygiene, University of Ulm, Germany.
Cancer Immunol Immunother. 1997 Jun;44(4):230-8. doi: 10.1007/s002620050378.
We demonstrate in a murine model that targeting an anti-viral T cell response to a growing tumor facilitates priming of a tumor-associated antigen (TAA)-specific, rejecting T cell response. Murine P815 mastocytoma cells grow aggressively in a syngeneic host. Transfected P815/S cells (expressing the hepatitis B surface antigen, HBsAg) also grow as subcutaneous tumors, but occasional 'spontaneous' rejections after transient growth are observed. Growth of P815/S tumors (but not of P815 tumors) is efficiently suppressed by a CD8+ cytotoxic T lymphocyte (CTL)-dependent immune mechanism in mice primed to HBsAg by DNA-immunization. In hosts immunized against HBsAg by DNA vaccination, HBsAg-specific CTL are generated. This specific CTL reactivity was targeted to s.c.-growing P815 tumors by intra tumor injections of either HBsAg-encoding plasmid DNA or viable P815/S cells; this treatment led to tumor rejection in 70-80% of the tumor-bearing animals. All rejecting animals showed a CD8+ CTL-dependent resistance to subsequent challenges by native, non-transfected P815 tumors. Targeting an established anti-viral ('strong') CTL response to a growing tumor hence is an efficient strategy to facilitate priming of a rejecting CTL response against ('weak') TAA in this system.
我们在小鼠模型中证明，将抗病毒T细胞反应靶向生长中的肿瘤有助于启动肿瘤相关抗原（TAA）特异性的排斥性T细胞反应。小鼠P815肥大细胞瘤细胞在同基因宿主中生长迅速。转染的P815/S细胞（表达乙肝表面抗原，HBsAg）也能作为皮下肿瘤生长，但在短暂生长后偶尔会观察到“自发”排斥现象。在通过DNA免疫对HBsAg致敏的小鼠中，P815/S肿瘤（而非P815肿瘤）的生长可被一种依赖CD8 + 细胞毒性T淋巴细胞（CTL）的免疫机制有效抑制。在通过DNA疫苗接种对HBsAg免疫的宿主中，会产生HBsAg特异性CTL。通过向肿瘤内注射编码HBsAg的质粒DNA或活的P815/S细胞，可使这种特异性CTL反应靶向皮下生长的P815肿瘤；这种治疗方法使70 - 80%的荷瘤动物出现肿瘤排斥。所有出现排斥的动物对随后天然的、未转染的P815肿瘤攻击均表现出依赖CD8 + CTL的抗性。因此，将已建立的抗病毒（“强”）CTL反应靶向生长中的肿瘤是在该系统中促进针对（“弱”）TAA的排斥性CTL反应启动的有效策略。
