Hirsch R, Ellenhorn J D, Bluestone J A
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892.
Princess Takamatsu Symp. 1988;19:237-43.
Anti-CD3 monoclonal antibodies (mAb) have been shown to suppress T cell-mediated immune responses both in vitro and in vivo. However, in vitro studies with these antibodies have also demonstrated that they possess potent mitogenic properties, raising the possibility that they might be capable of potentiating immune responses in vivo. In this regard, we have recently shown that an anti-CD3 mAb can activate murine T cells in vivo. Furthermore, low doses of antibody induce interleukin 2 (IL-2) receptor expression and enhanced proliferation to allogeneic major histocompatibility complex (MHC) antigen without detectable modulation or blocking of the T cell receptor and without suppression of T cell-mediated immune responses. In light of these findings, we investigated the ability of low dose anti-CD3 to enhance an anti-tumor response directed against the malignant murine UV-induced skin tumor, 1591-Pro-4L. Low dose anti-CD3 administration resulted in enhanced in vitro anti-tumor activity and prevented tumor outgrowth in approximately two-thirds of animals treated at the time of tumor inoculation. Furthermore, these animals displayed lasting tumor-specific immunity. These results suggest that anti-CD3 mAb can be utilized for the enhancement of anti-tumor responses in vivo and may have general application in the treatment of immunodeficiency.
抗CD3单克隆抗体(mAb)已被证明在体外和体内均可抑制T细胞介导的免疫反应。然而,对这些抗体的体外研究也表明它们具有强大的促有丝分裂特性,这增加了它们在体内可能增强免疫反应的可能性。在这方面,我们最近发现一种抗CD3 mAb可在体内激活小鼠T细胞。此外,低剂量抗体可诱导白细胞介素2(IL-2)受体表达,并增强对同种异体主要组织相容性复合体(MHC)抗原的增殖,而不会检测到T细胞受体的调节或阻断,也不会抑制T细胞介导的免疫反应。鉴于这些发现,我们研究了低剂量抗CD3增强针对恶性小鼠紫外线诱导的皮肤肿瘤1591-Pro-4L的抗肿瘤反应的能力。低剂量抗CD3给药导致体外抗肿瘤活性增强,并在大约三分之二肿瘤接种时接受治疗的动物中防止了肿瘤生长。此外,这些动物表现出持久的肿瘤特异性免疫。这些结果表明,抗CD3 mAb可用于增强体内抗肿瘤反应,可能在免疫缺陷治疗中有广泛应用。