Figure S1-S19 from Antibody–Exatecan Conjugates with a Novel Self-immolative Moiety Overcome Resistance in Colon and Lung Cancer

Abstract

<p>Supplementary Figure S1 shows Exatecan cytotoxicity and sensitivity to multidrug resistant genes. Supplementary Figure S2 shows Exatecan and DXd/SN-38 sensitivity to multidrug resistant genes. Supplementary Figure S3 shows Exatecan toxicity in rat. Supplementary Figure S4 shows the design and optimization of T moiety. Supplementary Figure S5 shows physicochemical and functional equivalence of Tras-GGFG-DXd and DS-8201a. Supplementary Figure S6 show physicochemical profile of antibody-exatecan conjugates enabled by T moiety. Supplementary Figure S7 shows additional T moiety-exatecan and belotecan conjugates. Supplementary Figure S8 shows in vitro and in vivo stability of MTX-1000. Supplementary Figure S9 shows cellular dynamics and mechanism of MTX-1000. Supplementary Figure S10 shows colon cancer organoid response to ADCs. Supplementary Figure S11 shows bystander killing effect of MTX-1000, T-DM1 and Tras-GGFG-DXd in coculture conditions in vitro. Supplementary Figure S12 shows hematology and serum chemistry of MTX-1000 in monkey. Supplementary Figure S13 shows T moiety-exatecan ADCs show potent antitumor efficacy and improved therapeutic index. Supplementary Figure S14 shows T moiety-exatecan ADCs show higher antitumor potency in PDX models and better intratumor pharmacodynamic response. Supplementary Figure S15 shows T moiety-exatecan ADCs overcome treatment-resistance due to improved therapeutic index and intratumor pharmacodynamic response. Supplementary Figure S16 shows overcoming MDR resistance by T moiety exatecan ADCs or a combination of MDR inhibitor with DXd/SN-38 ADCs. Supplementary Figure S17 shows Exatecan/MTX-1000 and PARP/ATR inhibitor synergize in colon cancer cells. Supplementary Figure S18 shows a patient-derived xenograft (PDX) model with EGFR triple mutation. Supplementary Figure S19 shows MTX-1000 induces immunological cell death and enhances antitumor immunity of anti-PD-1.</p>