Herlyn D, Linnenbach A, Koprowski H, Herlyn M
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Int Rev Immunol. 1991;7(4):245-57. doi: 10.3109/08830189109114874.
Anti-idiotypic antibodies (Ab2) that functionally mimic epitopes associated with human cancer cells are the most specific cancer vaccines currently available. Ab2 can induce specific humoral anti-tumor immunity in cancer patients. However, the potential of Ab2 for inducing cellular immunity in cancer patients still requires demonstration. Clonotypic antibodies directed against the combining site for tumor Ag on human T-cell clones may provide highly effective reagents for inducing protective T-cell immunity against human cancer. A new generation of cancer vaccines, molecularly cloned tumor-associated antigens (Ag), has recently been developed. Recombinant Ag have been successfully expressed in vectors allowing large scale production of Ag for immunization of cancer patients. Recombinant tumor Ag was shown to induce specific and protective immunity in experimental animals. In contrast to Ab2, which may mimic a single cancer-associated epitope, recombinant Ag express multiple epitopes that are potentially immunogenic. Ag vaccines, therefore, may be more effective in arresting tumor growth than single epitope (Ab2) vaccines because tumor destruction by antibodies is dependent on antibody density on tumor cell surfaces. In light of the important roles that both B and T cells play in the control of tumor growth, the demonstration of induction of specific B and T cell-immunity by recombinant tumor Ag and Ab2 in experimental animals is encouraging. Ultimately, the immunomodulatory role of both types of vaccines has to be compared in cancer patients who are immunologically tolerant to many Ag/epitopes expressed by their growing tumors. The development of both Ab2 and recombinant Ag for single antigenic systems provides the first step towards this goal.
能够在功能上模拟与人类癌细胞相关表位的抗独特型抗体（Ab2）是目前可用的最具特异性的癌症疫苗。Ab2可在癌症患者中诱导特异性体液抗肿瘤免疫。然而，Ab2在癌症患者中诱导细胞免疫的潜力仍有待证实。针对人类T细胞克隆上肿瘤抗原结合位点的克隆型抗体可能为诱导针对人类癌症的保护性T细胞免疫提供高效试剂。最近开发了新一代癌症疫苗，即分子克隆的肿瘤相关抗原（Ag）。重组抗原已在载体中成功表达，可大规模生产用于癌症患者免疫的抗原。重组肿瘤抗原在实验动物中显示可诱导特异性和保护性免疫。与可能模拟单个癌症相关表位的Ab2不同，重组抗原表达多个潜在具有免疫原性的表位。因此，抗原疫苗在阻止肿瘤生长方面可能比单表位（Ab2）疫苗更有效，因为抗体对肿瘤的破坏取决于肿瘤细胞表面的抗体密度。鉴于B细胞和T细胞在控制肿瘤生长中都发挥着重要作用，重组肿瘤抗原和Ab2在实验动物中诱导特异性B细胞和T细胞免疫的证明令人鼓舞。最终，必须在对其生长肿瘤表达的许多抗原/表位具有免疫耐受性的癌症患者中比较这两种疫苗的免疫调节作用。针对单一抗原系统开发Ab2和重组抗原是朝着这一目标迈出的第一步。
