Phase 1 Trial: STEAP1 CAR‑T Plus Enzalutamide A New Immune Approach for mCRPC

STEAP1 is a protein that sits on the surface of many prostate cancer cells, especially in advanced metastatic disease. Because it is abundant on cancer cells and much less present in normal tissues, STEAP1 looks like a promising “flag” that engineered immune cells can use to distinguish tumor from healthy organs.
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The treatment being studied is a form of CAR‑T cell therapy. In this approach, some of a patient’s T cells (a type of white blood cell that normally fights infections) are collected from the blood, then in the laboratory are given a new receptor that recognizes STEAP1 on prostate cancer cells. These modified cells are multiplied to large numbers and then infused back into the patient after a short course of chemotherapy that creates space in the immune system; once they find STEAP1, they become activated, release toxic substances, and can kill the cancer cells directly.

The preclinical program started with a “second‑generation” STEAP1 CAR design using a 4‑1BB costimulatory domain and CD3ζ signaling, similar to constructs that have already proven effective in blood cancers. In cell culture, these STEAP1 CAR‑T cells specifically recognized STEAP1‑positive prostate cancer lines, released interferon‑γ and other cytokines, and killed the cancer cells while sparing STEAP1‑negative controls. When tested in mouse models bearing human prostate tumors, a single dose of STEAP1 CAR‑T cells led to rapid tumor shrinkage and, in many animals, complete disappearance of measurable disease. In a disseminated 22Rv1 model, which mimics widespread metastatic cancer, treated mice survived roughly three times longer than untreated controls, and a significant proportion remained tumor‑free long term, a strong evidence of curative‑like activity in that preclinical setting.

These results were not limited to a single tumor type. The researchers work also showed activity across different STEAP1‑expressing models, including castration‑resistant prostate cancer lines, reinforcing that the target and the CAR design were not narrowly effective in just one cell line. Importantly, detailed pathology in these studies did not reveal clear off‑tumor tissue damage at effective doses, supporting the idea that STEAP1 expression is largely confined to malignant tissue and making on‑target, off‑tumor toxicity less likely than with some other solid‑tumor antigens.

Enzalutamide, the hormone‑blocking drug used together with the CAR‑T cells, is already a standard treatment for advanced prostate cancer. It works by strongly blocking the androgen receptor, the main switch that male hormones use to drive prostate cancer growth, and it can help control disease even after earlier hormone injections have stopped working. Laboratory studies suggest that blocking the androgen receptor can also change the tumor environment and stress cancer cells in ways that may make them more visible and vulnerable to immune attack, potentially helping the infused CAR‑T cells expand and stay active.

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