Abstract：
Immunotherapy has emerged as a promising approach to cancer treatment that utilizes the potential of the immune system to precisely identify and eradicate cancerous cells. Despite significant progress in immunotherapy, innovative approaches are required to enhance the effectiveness and safety of these treatments. Interleukin-12 (IL-12), widely recognized for its essential function in immune responses, has been explored as a potential candidate for treating cancer. However, early attempts involving the systemic administration of IL-12 were ineffective, with significant adverse effects, thus underscoring the need for innovation. To address these challenges, we developed a therapeutic molecule that utilizes a single-chain IL-12 mutant (IL-12mut) linked to a tumor-targeting arm. Here, we describe the development of a highly effective IL-12-based TMEkine™ platform by employing a B-cell lymphoma model (termed CD20-IL-12mut). CD20-IL-12mut combined the attenuated activities of IL-12 with targeted delivery to the tumor, thereby maximizing therapeutic potential while minimizing off-target effects. Our results revealed that CD20-IL-12mut exhibited potent anticancer activity by inducing complete regression and generating immunological memory for tumor antigens. Collectively, our data provide a basis for additional research on CD20-IL-12mut as a potential treatment choice for patients with B-cell lymphomas such as non-Hodgkin\'s lymphoma.
摘要：
免疫疗法已成为一种有前途的癌症治疗方法，它利用免疫系统的潜力来精确识别和根除癌细胞。尽管在免疫治疗方面取得了重大进展，需要创新的方法来提高这些治疗的有效性和安全性.白细胞介素-12(IL-12),因其在免疫反应中的基本功能而得到广泛认可，已被探索为治疗癌症的潜在候选者。然而,涉及全身给药IL-12的早期尝试无效，具有显著的不良影响，从而强调了创新的必要性。为了应对这些挑战，我们开发了一种治疗分子,该分子利用与肿瘤靶向臂连接的单链IL-12突变体(IL-12mut).这里,我们描述了通过使用B细胞淋巴瘤模型（称为CD20-IL-12mut）开发高效的基于IL-12的TMEkine™平台。CD20-IL-12mut结合减弱的IL-12活性与靶向递送到肿瘤，从而最大化治疗潜力,同时最小化脱靶效应。我们的结果表明，CD20-IL-12mut通过诱导完全消退并产生对肿瘤抗原的免疫记忆而表现出有效的抗癌活性。总的来说，我们的数据为进一步研究CD20-IL-12mut作为B细胞淋巴瘤如非霍奇金淋巴瘤患者的潜在治疗选择提供了基础.
