Srinivasan S, Yee N A, Wu K, Zakharian M, Mahmoodi A, Royzen M, Oneto J M Mejia
Shasqi, Inc., 665 3 St., Suite 501, San Francisco, CA 94107.
University of Albany, 1400 Washington Ave., LS-1136, Albany, NY 12222.
Adv Ther (Weinh). 2021 Mar;4(3). doi: 10.1002/adtp.202000243. Epub 2021 Jan 20.
While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. Our Click Activated Protodrugs Against Cancer (CAPAC™) Platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. We describe the benefits of SQ3370 (lead candidate of CAPAC) to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug™ of doxorubicin (Dox). SQ3370 was well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induced a systemic anti-tumor response against injected and non-injected lesions. The sustained anti-tumor response also correlated with immune activation measured at both lesions. SQ3370 could potentially benefit patients with micro-metastatic lesions.
虽然全身性免疫肿瘤疗法已取得显著成效，但只有有限的一部分患者从中受益。我们的点击激活抗癌前体药物（CAPAC™）平台是一种基于点击化学的方法，可在特定肿瘤部位激活抗癌药物，同时将全身毒性降至最低。CAPAC平台不受患者间可能存在差异的肿瘤特征影响，因此适用于多种类型的肿瘤。我们阐述了SQ3370（CAPAC的主要候选药物）在携带两种肿瘤的小鼠中实现全身抗肿瘤反应的益处。SQ3370由一种生物聚合物组成，注射到单个病灶中，随后全身给予阿霉素（Dox）的减毒前体药物™。SQ3370在常规Dox最大剂量的5.9倍时耐受性良好，使生存率提高了63%，并诱导了针对注射和未注射病灶的全身抗肿瘤反应。持续的抗肿瘤反应也与在两个病灶处测得的免疫激活相关。SQ3370可能使微转移病灶患者受益。
