Abstract:
Antibody-drug conjugates (ADCs) are fusions of therapeutic drugs and antibodies conjugated by a linker, designed to deliver a therapeutic payload to cells expressing the target antigen. By delivering the highly cytotoxic agent directly to cancer cells, ADCs are designed to enhance safety and broaden the therapeutic window. Recently, ADCs have demonstrated promising efficacy in various solid tumors and are rapidly expanding their indications. The prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor, with no new therapeutics since the advent of anti-PD-1 antibodies in 2016, highlighting a critical need for innovative therapies. Recent preliminary results suggest that ADCs could be promising treatment options for HNSCC as they explore a variety of target antigens, payloads, and linkers. However, for successful adaptation of ADCs in the treatment of HNSCC, addressing key challenges such as payload toxicities, antigen heterogeneity, and adaptive resistance will be essential. Current research focused on new ADC structures, including multispecific antibodies and noncytotoxic payloads, and diverse combination approaches, show promise for future advancements.
摘要:
抗体-药物缀合物(ADC)是治疗药物和通过接头缀合的抗体的融合体,设计用于将治疗性有效载荷递送至表达靶抗原的细胞。通过将高细胞毒性剂直接递送至癌细胞,ADC旨在提高安全性并拓宽治疗窗口。最近,ADC已在各种实体瘤中证明了有希望的功效,并且正在迅速扩大其适应症。晚期头颈部鳞状细胞癌(HNSCC)患者预后较差,自2016年抗PD-1抗体问世以来,没有新的治疗方法,这凸显了对创新疗法的迫切需求。最近的初步结果表明,ADC可能是HNSCC的有希望的治疗选择,因为它们探索了多种靶抗原,有效载荷,和接头。然而,为了成功适应ADC治疗HNSCC,解决有效载荷毒性等关键挑战,抗原异质性,适应性抵抗将是必不可少的。目前的研究集中在新的ADC结构,包括多特异性抗体和非细胞毒性有效载荷,和不同的组合方法,对未来的进步表现出希望。