Matsumura T, Krinock R A, Chang A E, Shu S
Department of Surgery, University of Michigan, Ann Arbor 48109.
Cancer Res. 1993 Sep 15;53(18):4315-21.
Cells from lymph nodes (LN) draining progressively growing tumors can differentiate into immune effector cells upon in vitro stimulation with anti-CD3 monoclonal antibodies followed by interleukin-2. The adoptive transfer of these activated LN cells to tumor-bearing mice mediates potent tumor-specific therapeutic effects. In this study, we sought to further characterize the antitumor efficacy and specificity mediated by the anti-CD3/IL-2 activated tumor-draining LN cells against heterologous clones derived from the murine MCA 106 sarcoma. Ten clones of divergent characteristics with regard to morphology, in vivo growth rate, ability to establish pulmonary metastases, MHC class I (H-2) antigen expression, susceptibility to lysis by allogeneic cytotoxic T-lymphocytes, as well as sensitivity to doxorubicin were selected and analyzed. In adoptive immunotherapy experiments, pulmonary metastases derived from each clone were found to be sensitive to the therapeutic effects of activated cells derived from LN draining the parental MCA 106 tumor. The antigenic cross-reactivity was evident from the observation that activated cells from LN draining each of the individual tumor clones were capable of mediating the regression of parental tumor metastases. The specificity of the antitumor reactivities mediated by LN cells draining MCA 106 clones was demonstrated by a lack of in vivo efficacy against metastases derived from the antigenically distinct MCA 205 sarcoma. Additionally, selected clones were tested for their ability to stimulate draining LN against other cloned tumors or used as targets for therapy with activated LN cells draining different clones. In all 29 adoptive immunotherapy experiments, there was complete cross-reactivity between different MCA 106 tumor clones. These findings suggest that the MCA 106 tumor-specific antigen(s) that stimulates draining LN in vivo and recognized by the anti-CD3/IL-2 activated cells is present on most if not all tumor cells. However, in the absence of a demonstrably resistant tumor clone, a very highly polymorphic antigen with many cross-reactive, but distinct epitopes might be operative and attributable to these observations.
引流逐渐生长肿瘤的淋巴结（LN）中的细胞，在用抗CD3单克隆抗体随后加白细胞介素-2进行体外刺激后，可分化为免疫效应细胞。将这些活化的LN细胞过继转移至荷瘤小鼠可介导强大的肿瘤特异性治疗效果。在本研究中，我们试图进一步表征抗CD3/IL-2活化的肿瘤引流LN细胞对源自小鼠MCA 106肉瘤的异源克隆所介导的抗肿瘤功效和特异性。选择并分析了10个在形态、体内生长速率、建立肺转移的能力、MHC I类（H-2）抗原表达、对同种异体细胞毒性T淋巴细胞裂解的敏感性以及对阿霉素的敏感性方面具有不同特征的克隆。在过继免疫治疗实验中，发现源自每个克隆的肺转移对引流亲本MCA 106肿瘤的LN中活化细胞的治疗效果敏感。抗原交叉反应性从以下观察结果中明显可见：引流各个肿瘤克隆的LN中的活化细胞能够介导亲本肿瘤转移的消退。引流MCA 106克隆的LN细胞所介导的抗肿瘤反应性的特异性通过对源自抗原性不同的MCA 205肉瘤的转移灶缺乏体内功效得以证明。此外，测试了所选克隆刺激引流LN对抗其他克隆肿瘤的能力，或用作来自不同克隆的活化LN细胞治疗的靶标。在所有29个过继免疫治疗实验中，不同的MCA 106肿瘤克隆之间存在完全的交叉反应性。这些发现表明，在体内刺激引流LN并被抗CD3/IL-2活化细胞识别的MCA 特异抗原，即便不是存在于所有肿瘤细胞上，也存在于大多数肿瘤细胞上。然而，在没有明显抗性肿瘤克隆的情况下，一种具有许多交叉反应但不同表位的高度多态性抗原可能起作用并可归因于这些观察结果。
