P1/2, N=48, Not yet recruiting, Fred Hutchinson Cancer Center | Initiation date: May 2024 --> Sep 2024

P1/2, N=48, Not yet recruiting, Fred Hutchinson Cancer Center

P1, N=441, Recruiting, Amgen | Trial completion date: Mar 2028 --> Jul 2028

In conclusion, the CD8sp_41BBz STEAP1 CAR T cells had superior expansion and survival in vitro and in vivo, compared to the IgGsp_CD28z counterpart, and a less exhausted phenotype upon repeated antigen exposure. Such persistence may be important for clinical efficacy.

P1, N=441, Recruiting, Amgen | Trial completion date: Jun 2028 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2026

In this review, we summarize the oncogenic functions of STEAP1 by cancer type. This review also provides new insights into the development of new anticancer strategies targeting STEAP1.

*N/A post-meeting for On Demand

Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer.

The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a mCRPC patient who achieved an objective response on AMG 509 treatment.

Preliminary PK showed dose-proportional increase in exposure with a mean terminal half-life of approximately 3-4 days. Conclusions Xaluritamig was tolerable with low-grade CRS (occurring primarily cycle 1) with encouraging preliminary efficacy in heavily pretreated pts with mCRPC.

By immunoblotting, it was confirmed that STEAP1 silencing induced the up-regulation of cathepsin B, intersectin-1, and syntaxin 4, and the down-regulation of HRas, PIK3C2A, and DIS3. These findings suggested that blocking STEAP1 might be a suitable strategy to activate apoptosis and endocytosis, and diminish cellular metabolism and intercellular communication, leading to inhibition of PCa progression.

Preliminary PK showed dose-proportional increase in exposure with a mean terminal half-life of approximately 3-4 days. Table: 1765O Lower DLs (DL 1–7) Higher DLs (DL8–15) Overall PSA evaluable N = 43 N = 46 N = 89 PSA ≥ 50%, n (%) 17 (39.5) 25 (54.3) 42 (47.2) PSA ≥ 90%, n (%) 8 (18.6) 16 (34.8) 24 (27.0) RECIST evaluable N = 30 N = 36 N = 66 PR, n (%) 1 (3.3) 14 (38.9) 15 (22.7) SD, n (%) 18 (60.0) 12 (33.3) 30 (45.5) Conclusions Xaluritamig was tolerable with low-grade CRS (occurring primarily cycle 1) with encouraging preliminary efficacy in heavily pretreated pts with mCRPC.

The MIP material showing a linear range from 130 pg/ml to 13 µg/ml. Overall, the biosensor exhibits essential properties such as selectivity, sensitivity and reproducibility for its application in medical and clinical research diagnosis and/or prognosis of prostate cancer.

No abstract available

STEAP1 antigen escape is a recurrent mechanism of treatment resistance and is associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein combined with STEAP1 CAR T cell therapy enhances antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading.

Besides, these chemotherapeutic drugs may stimulate the cell growth of PCa cells knocked down for STEAP1. In conclusion, this study demonstrated that STEAP1 expression levels might influence the response of PCa cells to chemotherapeutics drugs, indicating that the use of paclitaxel, docetaxel, or cabazitaxel may lead to harmful effects in PCa cells with decreased expression of STEAP1.

ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa.

Multiple iron metabolism related genes including STEAP1 and STEAP2 are significantly associated with the prognosis of LUAD patients. STEAP1 and STEAP2 might affect the prognosis of LUAD patients partially through immune cell infiltration, gene mutation and drug resistance, which indicated they were independent prognostic factors for LUAD patients.

In conclusion, the SwR confers CAR T cells with potent and durable in vitro functionality in TGFβ-rich environments. The SwR may be used as an add-on construct for CAR T cells or other forms of adoptive cell therapy.

P1, N=464, Recruiting, Amgen | Trial completion date: Nov 2027 --> Jun 2028 | Trial primary completion date: Nov 2025 --> Jun 2026

Overall, the cellular and molecular effects were similar between LNCaP wild‑type and LNCaP‑STEAP1 knockdown cells, except for c‑myc expression levels, where a cumulative effect between anti‑androgen treatment and STEAP1 knockdown was observed. The effect of STEAP1 knockdown alone or combined with anti‑androgens in c‑myc levels is required to be addressed in future studies.

Extracellular vesicles represent a promising biomarker to reduce the false positive rate of mpMRI in men with elevated PSA, potentially avoiding unnecessary biopsy and the associated morbidity. Our work will serve as scientific justification for validation studies and investigation of other EV-based biomarkers in an effort to further improve the ability to detect csPCa prior to biopsy.

EFEMP1 enabled the Wnt/β-catenin and TGF-β/Smad2/3 axises initiation and EMT elicitation by targeting STEAP1, thereby facilitating the osteosarcoma cell infiltration and migration. These results are expected to contribute to the search for new targeted drugs able to effectively inhibit invasion and metastasis and improve prognosis in osteosarcoma.

This quadrivalent immunotherapeutic approach using four antigens expressed in prostate cancer induced high magnitude, functional CD8+ T cells in murine models. The data suggest that comparing the intravenous versus intramuscular boosting routes is worthy of investigation in humans.

After a polishing step using the anion-exchanger Q-Sepharose, a highly pure, fully solubilized, and immunoreactive 35 kDa rhSTEAP1-His fraction was obtained. Altogether, the established reproducible strategy for the purification of rhSTEAP1-His paves the way to gather additional insights on structural, thermal, and environmental stability characterization significantly contributing for the elucidation of the functional role and oncogenic behavior of the STEAP1 in prostate cancer microenvironment.

A strategy of combining CBD-IL-12 together with STEAP1 CAR T cell therapy enhances anti-tumor responses by remodeling the TME and engaging host immunity. Ethics Approval All mouse studies were performed in accordance with protocols approved by the Fred Hutchinson Cancer Center Institutional Animal Care and Use Committee and regulations of Comparative Medicine.

In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

In prostate cancer, PSMA, STEAP1, TROP2, CD46 and B7-H3 are antigens currently being studied as targets for ADCs. In this paper, we discuss the composition of ADCs and focus on their application and challenges as treatment options in prostate cancer.

Here, the CAR T cells infiltrated tumors and significantly inhibited tumor growth and extended survival in a STEAP1-dependent manner. We conclude that the STEAP1 CAR exhibits potent in vitro and in vivo functionality and can be further developed toward potential clinical use.

In addition, STEAP1 was connected with increased chemosensitivity of drugs such as trametinib and pimasertib. STEAP1 was an underlying target for prognostic prediction in different cancer types and a potential biomarker of TMB, MSI, tumor microenvironment, and chemosensitivity.

STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

In addition, the involvement of HDAC in the regulation of STEAP1 mRNA expression was corroborated by a negative association between STEAP1 mRNA expression and HDAC4,5,7 and 9 in human PCa. In conclusion, our work indicates that STEAP1 overexpression in PCa can be driven by the hypomethylation of STEAP1 gene promoter.

A method for successfully isolating human STEAP1 from LNCaP cells was provided, avoiding the use of detergents to achieve stability, even outside a membrane-mimicking environment.

As results continue to emerge from these trials, understanding differential toxicity and efficacy of these therapies based on their targets and functional modifications will be key to advancing these promising therapies toward clinical practice. This review will provide a unique depth and breadth of perspective regarding the diverse immunotherapy strategies currently under clinical investigation for men with advanced prostate cancer.

Finally, chemotherapy and immune therapy responses for high- and low-risk patients were predicted. In conclusion, this study systematically analyzed the role of STEAP family in glioma and established a model for predicting therapy response in patients with glioma.

The sequential steps for invasion and metastasis were completed by an inverse association between functional barrier created by PD-L1 immunosuppressive molecule and EMT transcriptional factors. Our study implicates upregulation of EMT transcription factors to high proliferation rates, mechanical molecular barriers disassembly and increased cancer cell motility, as a critical molecular event leading to metastasis risk in PNENs thus emerging as a promising tool to select and customize therapy.

Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management...The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund's adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.

In conclusion, the knockdown of STEAP1 in liver cancer cell lines led to inhibition of cell proliferation involving G arrest by suppressing c-Myc. The present study provides a preclinical concept for STEAP1 as a druggable target in liver cancer.

This methodology could be a crucial starting point for large-scale production of active and stable conformation of recombinant human STEAP1. Thus, it could open up new strategies to unveil the structural rearrangement of STEAP1 and to better understand the biological role of the protein in cancer onset and progression.

Our results show that NKX2.2 is a co-regulator of STEAP1 expression and functions by interacting with the STEAP1 promoter at sites proximal to the reported EWSFLI1 sites. The co-operative interaction of NKX2.2 with EWSFLI1 in regulating STEAP1 holds potential as a new target for therapeutic interventions for ES.

Synthetic enhanced vaccines for prostate cancer antigens were shown to elicit antigen-specific immune responses in mice and the anti-tumor activity was evident in a prostate tumor challenge mouse model. These studies support further evaluation of the DNA tools for immunotherapy of prostate cancer and perhaps other cancers.