SUMMARY OF INVENTION
MSK researchers have developed an anti-STEAP1 T cell-engaging bispecific antibody (T-BsAb) which is highly efficient in driving T-cell infiltration and tumor ablation. STEAP1 (Six-Transmembrane Epithelial Antigen of Prostate 1) is upregulated in a variety of human cancers, including prostate, bladder, ovarian, rhabdomyosarcoma, and the Ewing family of tumors (EFT).
The expression of STEAP1 in normal tissues is highly restricted (with the exception of secretory tissues of the bladder and prostate). This makes it a very attractive target for antibody-based immunotherapies.
Impressive in vivo data has been generated to date in xenografts from EFT and prostate cancer.
- EFTs are an area of high unmet medical need as the prognosis is still poor despite use of high-dose chemotherapy and radiation treatment. Currently, cancer antigen-targeting immunotherapies largely have failed to induce effective T-cell receptor-mediated antitumor response.
- While several therapeutic strategies targeting STEAP1 for the treatment of prostate cancers are in early therapeutic trials, the most optimal platforms have yet to emerge.
Either as stand-alone therapeutic or for ex vivo armed T-cells, MSK’s novel anti-STEAP1 T-BsAb holds great therapeutic promise.
- The bispecific format chosen for MSK’s T-BsAb has been optimized and compared to multiple alternative formats
- Construct is effective against large established xenografts derived from EFT and prostate cancers
- Cross-reactivity of the MSK antibody between human, dogs, and non-human primates (NHP) will allow for use of dogs and NHP as models to assess not only the efficacy but also the on-target off-tumor toxicity
- MSK’s anti-STEAP1 T-BsAb showed exceptional antitumor efficacy compared with standard T-BsAb platforms in driving T-cells into tumors and suppressing tumor growth, enabling long-term disease-free survival
- EFTs represent the second-most-common malignant bone tumor in children and young adults; this remains an area of high unmet need with survival rates for metastatic or relapsed disease of less than 20%–30%. Given the high toxicities associated with intensive chemotherapy and radiotherapy, there is an urgent unmet need for novel therapeutic approaches. This T-cell-based immunotherapy is a promising alternative.
- Among U.S. men, prostate cancer is the second-leading cause of cancer-related death. STEAP1 is overexpressed in > 80% of prostate cancers, including bone and lymph node metastases. The prostate cancer space has one of the highest levels of unmet need among oncological indications, with few treatment options available for patients and chemotherapy continuing to dominate this market.
- PCT Application PCT/US2020/049377 filed on Sep 4, 2020. US National 17/640,598 filed on Mar 4, 2022.
- National applications filed in Canada, Europe, Australia, Israel, Japan, China and South Korea.
- Nai-Kong Cheung, MD, PhD. Laboratory Head, Memorial Hospital Research Laboratories; Enid A. Haupt Chair in Pediatric Oncology
- Lin, T-Y., et al. Novel potent anti-STEAP1 bispecific antibody to redirect T cells for cancer immunotherapy. J Immunother Cancer. 2021; 9(9): e003114. (PubMed link)
Imke Ehlers, PhD, CLP
Associate Director, Business Development and Licensing, Memorial Sloan Kettering Cancer Center, [email protected]