The Feasibility of Using Emerging Antibody-drug Conjugates for the Treatment of Small Cell Lung Cancer

Abstract

Antibody-drug conjugate (ADC) consists of three parts: antibodies, linkers, and cytotoxic payloads. With the deepening of research on ADC, the potential therapeutic effects of ADC on SCLC have also been emphasized. This study aims to evaluate and introduce five novel ADCs targeting small cell lung cancer (SCLC) and explore their anti-tumor activity, cytotoxicity, application prospects and so on. The first ADC drug is rovalpituzumab tesirine(Rova-T), currently, Rova-T has entered Phase Ⅲ clinical trial. The second drug is ABBV-011, and a study found that a single dose of ABBV-011 can lead to significant dose-dependent tumor regression in LU64. The third drug is NN2101-DM1, which is found to exhibit anti-tumor activity in xenograft mouse models. The fourth drug is D3-GPC2-PBD ADC. A study treated mice carrying NCI-H526(H526) xenografts with D3-GPC2-PBD ADC and found that the drug can lead to robust and sustained tumor regression, significantly improving the survival rate of mice without any side effects. The fifth study was on ADC targeting junctional adhesion molecule 3 Gene (JAM3), which found that SCLC cell lines typically express high levels of JAM3. The study also found that knocking down JAM3 can inhibit the growth of SCLC cells. Although these five ADCs are in different clinical trial stages, they all have inhibitory effects on SCLC.