RT Journal Article
SR Electronic
T1 SQ3370 Activates Cytotoxic Drug via Click Chemistry at Tumor and Elicits Sustained Responses in Injected & Non-injected Lesions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.13.337899
DO 10.1101/2020.10.13.337899
A1 Srinivasan, S.
A1 Yee, N. A.
A1 Wu, K.
A1 Zakharian, M.
A1 Mahmoodi, A.
A1 Royzen, M.
A1 Oneto, J.M. Mejia
YR 2020
UL http://biorxiv.org/content/early/2020/10/29/2020.10.13.337899.abstract
AB 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 antitumor 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.Competing Interest Statement- S. Srinivasan, N. A. Yee, M. Zakharian, A. Mahmoodi, J. M. Mejia Oneto are paid employees and shareholders of Shasqi, Inc. (Shasqi) - J.M. Mejia Oneto is the Founder and CEO of Shasqi. - M. Royzen is a shareholder of Shasqi.