ArticleInternational journal of molecular sciences2023
Generation and Characterization of SORT1-Targeted Antibody-Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
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- The Recycling Collagen Receptor uPARAP Is a Unique Mediator of Stromal Drug Delivery to Carcinoma Cells.Molecular cancer therapeutics · 2026Article
- Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics.Archives of pharmacal research · 2026Review
- Targeting uPARAP with an Antibody-Drug Conjugate Exhibits Efficacy against Mesothelioma and Synergizes with Cisplatin.Cancer research communications · 2026Article
- Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics.Archives of pharmacal research · 2026Review
- Dysfunctional Decidual CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Systematic screening of metabolic pathways to identify two breast cancer subtypes with divergent immune characteristics.Scientific reports · 2025Article
- Anti-tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models.Cancer science · 2024Article
- Neurotensin and Its Involvement in Female Hormone-Sensitive Cancers.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates (ADCs) have greatly improved the outcomes of advanced breast tumors. However, the treatment of breast tumors with existing ADCs is still hindered by many issues, such as tumor antigen heterogeneity and drug resistance. Therefore, ADCs against new targets would provide options for the treatment of these challenges. Sortilin-1 (SORT1) may be a promising target for ADC as it is upregulated in breast cancer. To evaluate the possibility of SORT1 as an ADC target, a humanized antibody_8D302 with high affinity against SORT1 was generated. Additionally, 8D302 was conjugated with MMAE and DXd to generate two ADCs_8D302-MMAE and 8D302-DXd, respectively. Both 8D302-MMAE and 8D302-DXd showed effective cytotoxicity against SORT1 positive breast tumor cell lines and induced bystander killing. Consequently, 8D302-MMAE showed relatively better anti-tumor activity than 8D302-DXd both in vitro and in vivo, but 8D302-DXd had superior safety profile and pharmacokinetics profile over 8D302-MMAE. Furthermore, SORT1 induced faster internalization and lysosomal trafficking of antibodies and had a higher turnover compared with HER2. Also, 8D302-DXd exhibited superior cell cytotoxicity and tumor suppression over trastuzumab-DXd, a HER2-targeted ADC. We hypothesize that the high turnover of SORT1 enables SORT1-targeted ADC to be a powerful agent for the treatment of SORT1-positive breast tumor.
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