腎細胞癌における抗イディオタイプ抗体の特異的免疫療法としての有用性

Abstract

Anti-idiotype antibody (Ab2) mimicking the nominal antigen (internal image Ab 2) may be useful as vaccine for malignancies. Six internal image Ab 2 (NUH 31 -91) were isolated directed against MAbG 250 which reacts with a large proportion of human renal cell carcinoma (RCC). Immunization of rabbits and mice with Ab 2 resulted in anti-anti-idiotype antibodies (Ab 3), which reacted with G 250-positive (G 250⁺) cell lysates but not with G 250-negative (G 250⁻) cell lysates, indicating the presence of specific anti-TAA antibody. Competitive RIA resulted in specific anti-TAA antibodies resembling MAbG 250 (Ab 1') in all Ab 3 sera, i. e., the immunization of mice and rabbits resulted in a specific humoral anti-TAA response. To investigate whether the immunization with Ab 2 could induce cell mediated immunity against antigen-positive cells, delayed type hypersen- sivity (DTH) tests were performed with G 250⁺ and/or G 250⁻ cells. For all six Ab 2, a profound DTH reaction was observed with G 250⁺ but not with G 250⁻ cells. The DTH responses could be transferred to naive mice by transfer of lymphocytes from. mice sensit- ized with Ab 2. These results indicate that mice and rabbits immunized with the Ab 2 mount antigen specific humoral and cellular responses. Fine specificity studies of mouse and rabbit Ab 3 sera revealed that the six Ab 2 could be divided into four mutually exclusive groups. Moreover, the anti-tumor efficacy of Ab 3 sera obtained from mice immunized with different internal image Ab 2 was investigated. Nu/nu BALB/c mice carrying small established NU 12 RCC xenografts or receiving a s. c. injection of 10^5 SK-RC-52 RCC cells were treated by i. p. injection of 0.2 ml Ab 3 sera. This treatment resulted in complete tumor rejection and significant tumor growth inhibition as compared to control groups (p ＜0.01). These findings demonstrate that immunization with Ab 2 elicits powerful anti- tumor effects in immune competent animals.