Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Matusz‐Fisher, Ashley; Tan, Antoinette R.

doi:10.21037/atm-22-1892

Cited by 3 publications

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Developing antibody-drug conjugates (ADCs) through coupling cytotoxic agents to antibodies has often proven to be a better therapeutic option for treating cancer compared to using antibodies alone, and more than 10 ADC agents have already been approved for clinical use [1]. In this regard, ADCs used in breast cancer treatment include Kadcyla and Enhertu, targeting human epidermal growth factor receptor 2 (HER2) [2], and Trodelvy, targeting trophoblast cell surface antigen-2 (TROP2) [3]. However, because of the heterogeneity of tumor antigens, existing ADCs do not cover all types of breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor

Zhuang,

Zhang,

Xie

et al. 2023

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor

Zhuang,

Zhang,

Xie

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

The Highs, Lows, and Resurgence of Antibody-drug Conjugates

Jackson

2024

JADC

View full text Add to dashboard Cite

Antibody-drug conjugates (ADCs) offer a way to deliver a cytotoxic or an immuno-stimulatory payload directly to tumors to maximize the anti-tumor efficacy of the payload with reduced systemic toxicities. Over several decades, the development of ADCs has cycled through highs and lows in which substantial excitement over the promise of ADCs was followed by disinterest when disappointing clinical results were announced. This has resulted in several companies abandoning their internal ADC development efforts. To date, 13 ADCs have been approved to treat hematologic or solid tumors, with 11 granted FDA approvals. Several ADC deals have been announced, which has reinvigorated interest and investments in ADCs. The renewed interest in ADCs is due, in part, to the recent clinical success of Daiichi Sankyo’s HER2-targeting ADC, trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo/AstraZeneca), which uses their proprietary topoisomerase I inhibitor payload, DXd. Enhertu is the first ADCs to gain US Food and Drug Administration’s (FDA) approval as a tissue-agnostic ADC, which provides optimism that more ADCs will be able to follow the success of trastuzumab deruxtecan.

show abstract

CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets

Maher

Davies

2023

Cancers

View full text Add to dashboard Cite

Immunotherapy with CAR T-cells has revolutionised the treatment of B-cell and plasma cell-derived cancers. However, solid tumours present a much greater challenge for treatment using CAR-engineered immune cells. In a partner review, we have surveyed data generated in clinical trials in which patients with solid tumours that expressed any of 30 discrete targets were treated with CAR-based immunotherapy. That exercise confirms that efficacy of this approach falls well behind that seen in haematological malignancies, while significant toxic events have also been reported. Here, we consider approximately 60 additional candidates for which such clinical data are not available yet, but where pre-clinical data have provided support for their advancement to clinical evaluation as CAR target antigens.

show abstract

Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer

Abstract: Matusz-Fisher A, Tan AR. Sacituzumab govitecan and other antibody-drug conjugates targeting trophoblast cell-surface antigen 2 (Trop-2) in breast cancer.

Cited by 3 publications

References 32 publications

Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor

Generation and Characterization of SORT1-Targeted Antibody–Drug Conjugate for the Treatment of SORT1-Positive Breast Tumor

The Highs, Lows, and Resurgence of Antibody-drug Conjugates

CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets

Contact Info

Product

Resources

About