Kactus Bio Expands STEAP Portfolio with Full-Length STEAP2 Protein for Targeted Cancer Therapeutics

STEAP is a family of six-transmembrane proteins, including four members STEAP1-4, widely involved in biological processes such as metal ion metabolism (e.g., iron and copper), cell proliferation, apoptosis, oxidative stress, and intercellular communication. They are expressed in various tissues and are overexpressed in multiple cancers, making them a highly regarded drug target in recent years.

STEAP2, full name Prostate Six-transmembrane Epithelial Antigen 2, like STEAP1, has also been found to be overexpressed in prostate cancer. The difference is that STEAP2 can shuttle between the cytoplasmic membrane and the trans-Golgi network, participating in both extracellular and intracellular pathways. STEAP2 not only possesses metal reductase activity (for example, it can reduce Fe³⁺Reduced to Fe²⁺), supplying metal ions to cells and promoting cell proliferation through different signaling pathways.Enhance the migration and invasion capabilities of cells.

Cellular Localization and Function of STEAP2 Protein^[1]

Compared with STEAP1, there are not many specific commercial antibodies for STEAP2. This may be due to the limited length of its extracellular loop, nearly complete conservation across species, and high homology with other STEAP family members. Although current research on STEAP1 is more in-depth, STEAP2 shows greater therapeutic potential and fewer side-effect risks due to its low expression in normal tissues and uniformly high expression in tumors. This gives STEAP2 unique advantages and broad application prospects in the treatment of prostate cancer.

AstraZeneca has a deep layout in the targeted drug development of STEAP2, involving ADC (AZD0516), CAR-T (AZD0754), and radiopharmaceuticals (²²⁵Ac-AZD2284) and TCE (AZD6621) in various forms.

Among them, AZD0516 is currently the only STEAP2 ADC under research, utilizing a degradable linker with Isatuximab as the payload. Preclinical data disclosed at the 2025 AACR conference demonstrated sustained tumor-killing effects in patient-derived xenograft models.^[2], with significant clinical development value, indicated for mCRPC.

The CAR-T drug AZD0754 is equipped with a dominant-negative transforming growth factor receptor II (dnTGFβRII).^[3], which is used to eliminate the immunosuppressive effects of the TGFβ signaling pathway. A Phase 1/2 clinical trial for metastatic prostate cancer is currently recruiting (NCT06267729), representing the most advanced STEAP2 pipeline from AstraZeneca.

Schematic Diagram of AZD0574 Mechanism^[3]

TCE AZD6621 adopts a special "0.5+1+2" design, incorporating a module that can bind to CD8, aiming to enhance CD8.⁺T cells undertake the killing function, reducing unnecessary cytokine release reactions.

“TED4” TCE: CD8 guiding arm; Affinity optimized anti-CD3^[4]

In addition, Regeneron has also laid out plans for monoclonal antibodies, bispecific antibodies, or ADCs targeting STEAP2, but they are still in the preclinical research stage. There have been no reports of STEAP2-targeting drugs in China.

STEAP1 has continuously achieved clinical success, and STEAP2 is increasingly gaining favor. The STEAP family has become a rising star in the field of oncology, while other members, including STEAP4, are also rapidly stepping into the spotlight.Following STEAP1, Kactus Biosystems successfully developed the full-length STEAP2 protein.White, expressed in mammalian cells, has a natural and complete conformation. Its biological activity has been rigorously validated and can meet the multi-scenario demands for STEAP2-related drug development.

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