Borrione P, Montacchini L, Beggiato E, Pileri A, Bianchi A, Massaia M
Università di Torino, Dipartimento di Medicine e Oncologia Sperimentale, Ospedale Molinette, Torino, Italy.
Leuk Lymphoma. 1996 Apr;21(3-4):325-30. doi: 10.3109/10428199209067615.
CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.
CD3 结合已被用作抗原特异性刺激的替代物，以触发 T 细胞效应功能。外源性白细胞介素 -2 已被用于延长和放大 CD3 诱导的 T 细胞活化。先前的研究表明，外周血中预激活（>10% HLA-DR+）T 细胞的癌症患者的 CD3 反应性增加。在本研究中，我们报告了 4 例晚期疾病且外周血中 HLA-DR+ T 细胞>10%的癌症患者[2 例多发性骨髓瘤（MM）、1 例 B 细胞淋巴瘤（NHL）、1 例转移性黑色素瘤（ME）]接受 9 个疗程的单次输注抗 CD3 单克隆抗体（OKT3），随后持续输注中等剂量白细胞介素 -2 的情况。治疗期间观察到淋巴细胞增加，在 CD4+和 CD8+亚群之间均匀分布。外周血中 CD25+细胞的出现从表型上证明了激活。出乎意料的是，功能研究[包括对有丝分裂原（PHA、OKT3）的增殖和细胞毒性测定（NK 和 LAK 活性）]与表型数据不一致，并且在 OKT3 和白细胞介素 -2 治疗后观察到所有功能略有下降。OKT3 和白细胞介素 -2 的输注耐受性良好，未观察到限制性毒性。该治疗在 2 例疾病进展的患者（NHL、ME）中未逆转肿瘤进展，对 2 例疾病稳定的 MM 患者仅有微小影响。这些数据表明，在这一小系列因外周血中 HLA-DR+ T 细胞数量增加而被选择进行治疗的晚期癌症患者中，序贯给予 OKT3 和白细胞介素 -2 没有抗肿瘤活性。在 CD25+ T 细胞的出现与临床结果之间观察到了差异。
