Monestier M, Debbas M E, Goldenberg D M
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Cancer Res. 1989 Jan 1;49(1):123-6.
BALB/c mice were immunized with either NP-3 or NP-4, two anticarcinoembryonic antigen murine monoclonal antibodies. Each animal produced anti-idiotype antibodies to the corresponding immunogen and no cross-reactivity between anti-NP-3 sera and anti-NP-4 sera was detected. Hybridomas were produced from these animals and two IgG1 anti-idiotype monoclonal antibodies were obtained: CM1 specific for NP-3 and CM11 specific for NP-4. CM1 and CM11 recognized determinants located within the antibody-combining site, since each anti-idiotype antibody inhibited the binding between the corresponding idiotype and carcinoembryonic antigens. Using an immunoblotting technique, neither CM1 nor CM11 reacted with isolated heavy or light chains of NP-3 or NP-4, whereas binding was observed with the intact molecule. This observation indicates that CM1 and CM11 are directed against conformational idiotypes resulting from the association of the variable regions of the heavy and light chains. Taken together, these results suggest that CM1 and CM11 might bear internal images of carcinoembryonic antigen epitopes, and that they are potential candidates as idiotype vaccines against colorectal tumors.
用两种抗癌胚抗原鼠单克隆抗体NP - 3或NP - 4免疫BALB/c小鼠。每只动物都产生了针对相应免疫原的抗独特型抗体,并且未检测到抗NP - 3血清与抗NP - 4血清之间的交叉反应。从这些动物中制备杂交瘤,获得了两种IgG1抗独特型单克隆抗体:针对NP - 3的CM1和针对NP - 4的CM11。CM1和CM11识别位于抗体结合位点内的决定簇,因为每种抗独特型抗体都抑制相应独特型与癌胚抗原之间的结合。使用免疫印迹技术,CM1和CM11均未与NP - 3或NP - 4的分离重链或轻链发生反应,而与完整分子发生了结合。这一观察结果表明,CM1和CM11针对的是由重链和轻链可变区缔合产生的构象独特型。综上所述,这些结果表明CM1和CM11可能携带癌胚抗原表位的内影像,并且它们是作为抗结直肠癌独特型疫苗的潜在候选物。