INSERM Unite Mixte de Recherche (UMR) S872, Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, 15 rue de l'Ecole de Medecine, Paris, France.
Blood. 2010 Aug 12;116(6):926-34. doi: 10.1182/blood-2009-10-248609. Epub 2010 May 3.
The anti-CD20 monoclonal antibody (mAb) rituximab has been used successfully for lymphoma therapy for more than 10 years. Although several direct mechanisms by which anti-CD20 mAbs act have been characterized in vitro, their specific role in clinical efficacy is still debated. Little is known about the possible antitumor immune response that they may induce in patients, despite clinical data suggesting a "vaccinal" effect. We show here that an initial treatment with anti-CD20 induces protection against human CD20-expressing tumor cells and allows immunocompetent mice to survive tumor challenge. This long-lasting protection requires the presence of the Fc portion of the anti-CD20 mAb and is achieved through the induction of a cellular immune response. Only CD4(+) cells were needed at the beginning of the treatment, but both CD4(+) and CD8(+) cells were required after tumor challenge to achieve protection. Finally, we show that interleukin-2 treatment, given after tumor challenge, improves the overall survival rate, compared with that obtained by anti-CD20 treatment alone. These findings demonstrate that anti-CD20 mAbs exert therapeutic effects through the induction of an adaptive cellular immune response, aside from any direct mechanisms involving effectors from innate immunity.
抗 CD20 单克隆抗体（mAb）利妥昔单抗已成功用于淋巴瘤治疗超过 10 年。尽管已经在体外鉴定出抗 CD20 mAb 的几种直接作用机制，但它们在临床疗效中的具体作用仍存在争议。尽管临床数据表明存在“疫苗”效应，但对于它们可能在患者中诱导的抗肿瘤免疫反应知之甚少。我们在这里表明，初始抗 CD20 治疗可诱导对人 CD20 表达肿瘤细胞的保护，并使免疫功能正常的小鼠能够存活肿瘤挑战。这种持久的保护需要抗 CD20 mAb 的 Fc 部分的存在，并通过诱导细胞免疫反应来实现。在治疗开始时仅需要 CD4(+)细胞，但在肿瘤挑战后需要 CD4(+)和 CD8(+)细胞来实现保护。最后，我们表明，与单独使用抗 CD20 治疗相比，在肿瘤挑战后给予白细胞介素 2 治疗可提高总生存率。这些发现表明，抗 CD20 mAb 通过诱导适应性细胞免疫反应发挥治疗作用，除了涉及先天免疫效应物的任何直接机制之外。
