Dyer M J, Hale G, Marcus R, Waldmann H
a Departments of Haematology and Pathology, University of Cambridge, Cambridge, UK.
Leuk Lymphoma. 1990;2(3-4):179-93. doi: 10.3109/10428199009053522.
CAMPATH-1 (CDw52) antigen is a heavily glycosylated, non-modulating glycoprotein expressed abundantly on the cell surface of nearly all normal and malignant lymphocytes but not on hemopoietic stem cells. A series of rat monoclonal antibodies (MAbs) with CDw52 specificity but of varying immunoglobulin isotype has been produced, and assessed for ability to deplete lymphoid cells in patients with lymphoproliferative disorders. Although all IgM, IgG2a and IgG2b rat MAbs were able to elicit lysis with human complement in vitro, only the IgG2b MAb (CAMPATH-1G) could elicit substantial lymphoid depletion in vivo. The efficacy of CAMPATH-1 G probably results from its ability to bind human Fc receptors and activate cell-mediated lysis of antibody-coated cells. Twenty-nine patients with lymphoid malignancies have received between 250 mg and 680 mg of CAMPATH-1G; nine of these attained complete remission A human MAb with CDw52 specificity has been produced by "grafting" the complementarity-determining regions (CDRs) of the rat MAb into human IgG1 heavy- and kappa light-chain genes. These constructs were transfected into a rat myeloma cell line. Sufficient human MAb (CAMPATH-1H) has been purified to treat two patients with non-Hodgkin's lymphoma in leukemic phase. Although each patient only received approximately 100 mg of MAb, remission was induced in both patients with recovery of normal hemopoiesis during the course of therapy CDw52 MAbs are the first MAbs to demonstrate consistent anti-tumor effects in vivo and may have roles in the therapy of a wide range of lymphoid malignancies and as powerful immunosuppressive agents.
CAMPATH-1（CDw52）抗原是一种高度糖基化、非调节性糖蛋白，在几乎所有正常和恶性淋巴细胞的细胞表面大量表达，但在造血干细胞上不表达。已制备出一系列具有CDw52特异性但免疫球蛋白同种型不同的大鼠单克隆抗体（MAb），并评估了它们在淋巴增殖性疾病患者中清除淋巴细胞的能力。尽管所有IgM、IgG2a和IgG2b大鼠MAb在体外都能与人补体引发细胞溶解，但只有IgG2b MAb（CAMPATH-1G）能在体内引发显著的淋巴细胞清除。CAMPATH-1G的疗效可能源于其结合人Fc受体并激活抗体包被细胞的细胞介导溶解的能力。29例淋巴恶性肿瘤患者接受了250毫克至680毫克的CAMPATH-1G；其中9例实现了完全缓解。通过将大鼠MAb的互补决定区（CDR）“移植”到人IgG1重链和κ轻链基因中，制备出了一种具有CDw52特异性的人MAb。这些构建体被转染到大鼠骨髓瘤细胞系中。已纯化出足够的人MAb（CAMPATH-1H）来治疗2例白血病期非霍奇金淋巴瘤患者。尽管每位患者仅接受了约100毫克的MAb，但两名患者均诱导出缓解，且在治疗过程中正常造血功能得以恢复。CDw52 MAb是首批在体内表现出一致抗肿瘤作用的MAb，可能在多种淋巴恶性肿瘤的治疗中发挥作用，并作为强大的免疫抑制剂。
