HER2 Antibody-Nanogel Conjugates: A High-Capacity, Antibody-Sparing Alternative to Antibody-Drug Conjugates.

Abstract

HER2-targeted antibody-nanogel conjugates (ANCs) were developed with covalently encapsulated DM1 and benchmarked against the clinically optimized antibody-drug conjugate Kadcyla (T-DM1). In vitro, ANCs showed cytotoxicity comparable to that of T-DM1. In vivo, despite being at the proof-of-concept stage, HER2-DM1-ANC achieved equivalent antitumor efficacy in a BT-474 breast cancer xenograft model while requiring 4-fold less antibody. This reduced antibody usage may lessen the risk of tumor resistance, highlighting the unique advantage of the nanogel platform. The benefit stems from ANCs' higher drug-to-antibody ratio, achieved without chemical modification of the payload─a key bottleneck in ADC development. While T-DM1 represents a mature clinical product, these findings underscore ANCs as a high-capacity, modular nanoscale platform with significant potential for refinement and optimization in antibody-directed therapeutics.