Moini Katayoun, Seery Tara, Nangia Chaitali, MacDiarmid Jennifer, Brahmbhatt Himanshu, Spilman Patricia, Sender Lennie, Soon-Shiong Patrick
Chan Soon-Shiong Institute for Medicine (CSSIFM), El Segundo, CA 90245, United States.
EnGeneIC, Ltd., North Ryde, Sydney, NSW 2113, Australia.
Oncologist. 2025 Mar 10;30(3). doi: 10.1093/oncolo/oyae267.
Multimodal temporal therapy orchestrated to leverage immunotherapy, tumor-targeted chemotherapy, and natural killer (NK) cell therapy may provide an opportunity to induce immunogenic cell death for tumor response and increased survival in patients with recurrent cancer. The interleukin-15 (IL-15) superagonist N-803, an enhancer of NK cells, CD4 + T cells, cytotoxic CD8 + T cells, and memory T-cell activity, combined with off-the-shelf PD-L1-targeted high-affinity NK (PD-L1 t-haNK) cells represent novel immunotherapies designed to overcome an immunosuppressive tumor microenvironment (TME). The epidermal growth factor receptor-targeted antibody-nanocell conjugate E-EDV-D682 provides tumor-targeted chemotherapy in the form of its anthracycline metabolite PNU159682 (nemorubicin) cargo and is currently being studied in combination with immunomodulatory EDVs delivering the adjuvant α-galactosyl ceramide (GC). Here, we report the compassionate use treatment of this combination in a patient with recurrent, metastatic pancreatic cancer (mPC) after 3 lines of therapy. Under the initial single-patient Investigational New Drug (spIND) protocol, the patient received N-803, PD-L1 t-haNK cells, and the albumin doxorubicin conjugate aldoxorubicin for ~27 months. The patient's disease became stable on this regimen, and a transient complete response was observed by ~14 months of therapy. Due to progression, a second spIND protocol was designed whereby the patient received E-EDV-D682 plus EDV-GC for more than 24 months, which resulted in stable disease and the patient's continued survival at the time this report was written. The patient's extended survival despite the dire prognosis associated with recurrent mPC points to the merits of this temporal combination regimen in overcoming immuno-chemo resistance with enhanced immune activity required for tumor response and extended survival.
精心安排以利用免疫疗法、肿瘤靶向化疗和自然杀伤（NK）细胞疗法的多模式时间疗法，可能为诱导免疫原性细胞死亡以实现肿瘤反应并提高复发癌患者的生存率提供机会。白细胞介素-15（IL-15）超级激动剂N-803是一种NK细胞、CD4 + T细胞、细胞毒性CD8 + T细胞和记忆T细胞活性的增强剂，与现成的靶向PD-L1的高亲和力NK（PD-L1 t-haNK）细胞联合使用，代表了旨在克服免疫抑制性肿瘤微环境（TME）的新型免疫疗法。表皮生长因子受体靶向抗体-纳米细胞偶联物E-EDV-D682以其蒽环类代谢产物PNU159682（奈莫柔比星）为载体提供肿瘤靶向化疗，目前正在与递送佐剂α-半乳糖神经酰胺（GC）的免疫调节性EDV联合进行研究。在此，我们报告了该联合疗法在一名经过3线治疗的复发性转移性胰腺癌（mPC）患者中的同情用药治疗情况。根据最初的单人研究性新药（spIND）方案，该患者接受了N-803、PD-L1 t-haNK细胞和白蛋白阿霉素偶联物醛氧阿霉素治疗约27个月。患者的疾病在该治疗方案下趋于稳定，在治疗约14个月时观察到短暂的完全缓解。由于病情进展，设计了第二个spIND方案，患者接受E-EDV-D682加EDV-GC治疗超过24个月，这导致疾病稳定，并且在撰写本报告时患者仍持续存活。尽管复发性mPC预后不佳，但该患者的生存期延长，这表明这种时间联合治疗方案在克服免疫化疗耐药性方面具有优势，具有肿瘤反应和延长生存期所需的增强免疫活性。
