Development of a facile antibody–drug conjugate platform for increased stability and homogeneity

Gupta, Nimish ; Kancharla, Johny ; Kaushik, Shelly ; Ansari, Aasif ; Hossain, Samad ; Goyal, Ravinder ; Pandey, Manoj ; Sivaccumar, Jwala ; Hussain, Sazid ; Sarkar, Arindam ; Sengupta, Aniruddha ; Mandal, Swadhin K. ; Roy, Monideepa ; Sengupta, Shiladitya (2017) Development of a facile antibody–drug conjugate platform for increased stability and homogeneity Chemical Science, 8 (3). pp. 2387-2395. ISSN 2041-6520

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Official URL: http://doi.org/10.1039/C6SC05149A

Related URL: http://dx.doi.org/10.1039/C6SC05149A

Abstract

Despite the advances in the design of antibody–drug conjugates (ADCs), the search is still ongoing for novel approaches that lead to increased stability and homogeneity of the ADCs. We report, for the first time, an ADC platform technology using a platinum(II)-based linker that can re-bridge the inter-chain cysteines in the antibody, post-reduction. The strong platinum–sulfur interaction improves the stability of the ADC when compared with a standard maleimide-linked ADC thereby reducing the linker–drug exchange with albumin significantly. Moreover, due to the precise conserved locations of cysteines, both homogeneity and site-specificity are simultaneously achieved. Additionally, we demonstrate that our ADCs exhibit increased anticancer efficacy in vitro and in vivo. The Pt-based ADCs can emerge as a simple and exciting proposition to address the limitations of the current ADC linker technologies.

Item Type:Article
Source:Copyright of this article belongs to Royal Society of Chemistry.
ID Code:118293
Deposited On:19 May 2021 19:56
Last Modified:19 May 2021 19:56

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