Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China.
Sci Adv. 2020 Mar 4;6(10):eaaz4204. doi: 10.1126/sciadv.aaz4204. eCollection 2020 Mar.
Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several "cocktail" therapeutic formulations by mixing immunogenic cell death (ICD)-inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.
目前，人们迫切需要开发具有降低全身毒性和强效疗效的化学免疫疗法，以对抗具有扩散转移的晚期癌症。在这里，我们报告了几种通过将免疫原性细胞死亡（ICD）诱导化疗药物和免疫佐剂与藻酸盐（ALG）混合在一起用于局部化学免疫治疗的“鸡尾酒”治疗制剂。免疫检查点阻断（ICB）抗体可以包含在这种鸡尾酒中进行局部注射，也可以通过常规静脉注射使用。将这种鸡尾酒注入实体瘤后，ALG 的原位凝胶化将导致治疗药物的局部保留和持续释放，以降低全身毒性。在免疫佐剂的帮助下，化疗引起的 ICD 会引发肿瘤特异性免疫反应，这些反应进一步被 ICB 放大，从而引发强烈的全身抗肿瘤免疫反应，破坏局部肿瘤、消除转移和抑制癌症复发。我们将临床使用的药物联合用于肿瘤局部鸡尾酒化学免疫疗法的策略具有很大的临床转化潜力。
