RE:ADC targeting SORT1 extract from the study...re dosage
Previous studies had shown that SORT1 was overexpressed in breast cancer cells and underexpressed in normal cells [17]. Our results demonstrated that the surface of breast cancer cells was localized with a large amount of SORT1, while it was not present on the surface of non-tumor breast cell_MCF-10A. The expression profile supported SORT1 as a potential target for new ADC development. In addition, a SORT1-targeted PDC-TH1902 is now evaluated in clinical environments to treat TNBC. The PDC demonstrated significant efficacy and good safety in preclinical studies [19]. However, TH1902 required multiple high-dosage injections to completely inhibit the growth of tumor growth in MDA-MB-231 xenograft mice. On the contrary, 8D302-DXd showed complete inhibition at one dose of 10 mg/kg. This may be due to relatively short half-life of PDC in vivo. TH1902 has only 1.44 h of half-life in mice, while the half-life of ADC in mice is usually more than 48 h [35]. In this study, the half-life of 8D302-DXd and 8D302-MMAE were 62.3 and 222.9 h, respectively. Furthermore, 8D302-DXd exhibited brilliant a safety profile with no significant effect on mice body weight at a dose of 100 mg/kg. This suggests that ADC may be a better form for SORT1-targeted drugs compared with PDC.
LouisW wrote: https://www.mdpi.com/1422-0067/24/24/17631
This china group is seemingly interested in SORT1, they pulished another paper to investigate the performace of mAb targeting Her2 and SORT1. I agree SORT1 is a highly potential target, question is whether TH1902 can reproduce the phenomena that Th observed in rodent in human.
Previous studies had shown that SORT1 was overexpressed in breast cancer cells and underexpressed in normal cells [17]. Our results demonstrated that the surface of breast cancer cells was localized with a large amount of SORT1, while it was not present on the surface of non-tumor breast cell_MCF-10A. The expression profile supported SORT1 as a potential target for new ADC development. In addition, a SORT1-targeted PDC-TH1902 is now evaluated in clinical environments to treat TNBC. The PDC demonstrated significant efficacy and good safety in preclinical studies [19]. However, TH1902 required multiple high-dosage injections to completely inhibit the growth of tumor growth in MDA-MB-231 xenograft mice. On the contrary, 8D302-DXd showed complete inhibition at one dose of 10 mg/kg. This may be due to relatively short half-life of PDC in vivo. TH1902 has only 1.44 h of half-life in mice, while the half-life of ADC in mice is usually more than 48 h [35]. In this study, the half-life of 8D302-DXd and 8D302-MMAE were 62.3 and 222.9 h, respectively. Furthermore, 8D302-DXd exhibited brilliant a safety profile with no significant effect on mice body weight at a dose of 100 mg/kg. This suggests that ADC may be a better form for SORT1-targeted drugs compared with PDC.