Immuno-oncology is revolutionizing the treatment of cancers, by inducing the recognition and elimination of tumor cells by the immune system. Recent advances have focused on generating or unleashing tumor antigen-specific T-cell responses, leading to alternative treatment paradigms for many cancers. Despite these successes, the clinical benefit has been limited to a subset of patients and certain tumor types, highlighting the need for alternative strategies. One innovative approach is to broaden and amplify antitumoral immune responses by targeting innate immunity. Particularly, the aim has been to develop new antibody formats capable of stimulating the antitumor activity of innate immune cells, boosting not only their direct role in tumor elimination, but also their function in eliciting multicellular immune responses ultimately resulting in long-lasting tumor control by adaptive immunity. This review covers the development of a new class of synthetic molecules, natural killer cell engagers (NKCEs), which are built from fragments of monoclonal antibodies (mAbs) and are designed to harness the immune functions of NK cells in cancer. As currently shown in preclinical studies and clinical trials, NKCEs are promising candidates for the next generation of tumor immunotherapies.

中文翻译：

---

自然杀伤细胞参与癌症免疫治疗：下一代免疫肿瘤治疗

免疫肿瘤学通过诱导免疫系统识别和消除肿瘤细胞，正在彻底改变癌症的治疗。最近的进展集中在产生或释放肿瘤抗原特异性 T 细胞反应，导致许多癌症的替代治疗范式。尽管取得了这些成功，但临床获益仅限于一部分患者和某些肿瘤类型，这凸显了对替代策略的需求。一种创新方法是通过靶向先天免疫来扩大和放大抗肿瘤免疫反应。特别是，目标是开发新的抗体形式，能够刺激先天免疫细胞的抗肿瘤活性，不仅增强它们在消除肿瘤中的直接作用，以及它们在引发多细胞免疫反应方面的功能，最终通过适应性免疫实现持久的肿瘤控制。本综述涵盖了一类新的合成分子——自然杀伤细胞接合体 (NKCE) 的开发，该分子由单克隆抗体 (mAb) 的片段构建而成，旨在利用癌症中 NK 细胞的免疫功能。正如目前临床前研究和临床试验所示，NKCE 是下一代肿瘤免疫疗法的有希望的候选者。