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Target Overview
STEAP2 is a 6 transmembrane receptor that is a member of the STEAP family of metalloreductases. STEAP2 has been found to be highly overexpressed across all stages of prostate adenocarcinoma1 and its role in promoting aggressive cancer traits2, its relatively homogeneous cell surface expression in prostate cancer and limited expression in normal tissue1 make STEAP2 an attractive therapeutic target for a T cell engager.
Compound Overview
AZD6621 is an investigational trispecific T cell engager, which incorporates 2 Fab binding domains to STEAP2, one Fab binding domain to CD3 and one VHH binding domain to CD8. The CD8 and CD3 domains enable preferential engagement of CD8+ T cells, with the potential to give a broad therapeutic index by reducing CD4+ T cell-associated cytokine release3.
Mechanism of Action
References
1. Zanvit P, van Dyk D, Fazenbaker C, et al. J Clin Invest. 2023;133(22). 2. Burnell SEA, Spencer-Harty S, Howarth S, et al. Sci Rep. 2018;8(1):6252. 3. Sitnikova S, Burrows N, Ioannou N, et al. Cancer Res. 2025;85(8_Supplement_1):3514.
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Abbreviations
CD3
cluster of differentiation 3
CD4+
cluster of differentiation 4+
CD8
cluster of differentiation 8
Fab
fragment antigen-binding
mCRPC
metastatic castration-resistant prostate cancer
RDE
recommended dose for expansion
STEAP2
six-transmembrane epithelial antigen of prostate-2
VHH
variable domain of the heavy-chain
Target Overview
STEAP2 is a 6 transmembrane receptor that is a member of the STEAP family of metalloreductases. STEAP2 has been found to be highly overexpressed across all stages of prostate adenocarcinoma1 and its role in promoting aggressive cancer traits2, its relatively homogeneous cell surface expression in prostate cancer and limited expression in normal tissue1 make STEAP2 an attractive therapeutic target for a T cell engager.
Compound Overview
AZD6621 is an investigational trispecific T cell engager, which incorporates 2 Fab binding domains to STEAP2, one Fab binding domain to CD3 and one VHH binding domain to CD8. The CD8 and CD3 domains enable preferential engagement of CD8+ T cells, with the potential to give a broad therapeutic index by reducing CD4+ T cell-associated cytokine release3.
Mechanism of Action
References
1. Zanvit P, van Dyk D, Fazenbaker C, et al. J Clin Invest. 2023;133(22). 2. Burnell SEA, Spencer-Harty S, Howarth S, et al. Sci Rep. 2018;8(1):6252. 3. Sitnikova S, Burrows N, Ioannou N, et al. Cancer Res. 2025;85(8_Supplement_1):3514.
Clinical trial information
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Abbreviations
CD3
cluster of differentiation 3
CD4+
cluster of differentiation 4+
CD8
cluster of differentiation 8
Fab
fragment antigen-binding
mCRPC
metastatic castration-resistant prostate cancer
RDE
recommended dose for expansion
STEAP2
six-transmembrane epithelial antigen of prostate-2
VHH
variable domain of the heavy-chain