Chapter 11 - CT16: A dual antibody targeting both EGFR and Notch suppresses EGFR blockage and radiation resistance by decreasing tumor-initiating cell frequency

Abstract

EGFR-targeted treatment and radiation have certain curative effects on cancer, but the accompanying resistance is an intractable problem. Existing studies have shown that abnormal Notch signaling and the expansion of cancer stem cells may be closely related to this problem. Therefore, in this chapter, researchers conducted a dual-targeting antibody, CT16, targeting both EGFR and Notch2/3 receptors, in addition to blocking the activation of these two receptors while inhibiting the expansion of stem-like tumor cells. The results of in vitro and in vivo experiments showed that CT16 effectively inhibited the resistance of nonsmall cell lung cancer (NSCLC) cell lines and patient-derived xenograft (PDX) tumor models to EGFR inhibitors and radiation and enhanced the sensitivity to radiation. The enhancement effect is better than that of EGFR inhibitors or tarextumab combined with radiation. Significantly, CT16 was able to effectively reduce the proliferation of the stem-like cell subpopulation. This study aimed to characterize a dual antibody targeting EGFR and Notch2/3 signaling and recommend its potential clinical value in combination with radiotherapy for the treatment of malignant tumors.