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。尽管免疫疗法取得了重大进展，但仍需要创新方法来提高这些治疗的有效性和安全性。白介素 12 (IL-12) 因其在免疫反应中的重要功能而被广泛认可，已被探索作为治疗癌症的潜在候选药物。然而，涉及IL-12全身给药的早期尝试是无效的，并具有显着的副作用，因此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相连的单链 IL-12 突变体 (IL-12mut)。在这里，我们描述了通过采用 B 细胞淋巴瘤模型（称为 CD20-IL-12mut）开发基于 IL-12 的高效 TMEkine™ 平台。 CD20-IL-12mut 将 IL-12 的减弱活性与靶向递送至肿瘤相结合，从而最大限度地提高治疗潜力，同时最大限度地减少脱靶效应。我们的结果表明，CD20-IL-12mut 通过诱导肿瘤抗原的完全消退和产生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 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的进一步研究提供了基础。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

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.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.