LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hello fellow warriors! Ok, the AACR 2026 meeting has passed, but in a month the ASCO 2026 annual meeting will begin. There will be new interesting research to share!
Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• Phase 1 Trial: Double-Masked PSMA-TCE JANX014 Enters Testing for mCRPC​
  ​JANX014 is a novel T-cell engager that has entered its first-in-human clinical trial for patients with metastatic castration-resistant prostate cancer (mCRPC). It utilizes a dual-masking design on both its PSMA-binding and CD3 T-cell recruiting domains to ensure the drug only activates within the protease-rich environment of a tumor. This strategy is intended to redirect cytotoxic T cells against cancer cells while minimizing systemic cytokine release syndrome, a common side effect of similar therapies. The trial evaluates safety and early anti-tumor activity through ascending intravenous doses.
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• Phase 1/2 Trial: AZD8359, a CD8-Biased Trispecific T Cell Engager for mCRPC​
  ​AZD8359 is a trispecific T-cell engager entering clinical testing through the CRIUS-1 study to treat patients with mCRPC. Unlike conventional engagers that trigger broad immune activation, AZD8359 uses the TITAN platform to selectively recruit cytotoxic CD8+ T cells while largely ignoring CD4+ T helper cells, which are primarily responsible for cytokine release syndrome. Preclinical data showed that this molecule achieved complete regressions in bone metastasis models, which are typically difficult for immunotherapies to penetrate. The drug targets STEAP2, a protein expressed almost exclusively in prostate tissue across all stages of the disease.
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• Phase 1/2 Trial: RAISIC-1 Evaluating GPR65 Inhibitor PTT-4256​
  The RAISIC-1 trial is a modular study assessing PTT-4256, a first-in-class small-molecule inhibitor of the proton-sensing receptor GPR65. GPR65 acts as an acid-sensing immune checkpoint that normally weakens immune cell activity in the acidic microenvironment of a tumor. By blocking this receptor, PTT-4256 aims to “normalize” the tumor microenvironment, re-arming T-cells and NK-cells to fight the cancer. The Phase 1/2 study includes patients with advanced solid tumors, including those with castration-resistant prostate cancer.​
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• A New Integrated Prognostic Score for Cabazitaxel Use​
  Physicians may now be able to better identify which patients will benefit from cabazitaxel using a new integrated prognostic score called the “cabascore”. This tool uses six routine clinical factors—such as PSA levels, performance status, and hemoglobin—to divide patients into favorable, intermediate, and poor risk categories. Validation in major Phase 3 trials showed that while favorable-risk patients derive a clear survival advantage from cabazitaxel, those in higher-risk groups may not benefit to the same degree. This suggests that delivering cytotoxic therapy while patients are still physiologically robust is critical for the best outcome.
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Preclinical Research & Reviews

• PSMA-Targeted CAR-T Cell Therapy with CD16A Signaling​
  A new study has designed a PSMA-targeted CAR-T cell therapy that utilizes CD16A as its sole signaling part to combat the immune suppression often found in solid tumors. In preclinical mouse models, this design led to a 36.6% increase in median overall survival and visible tumor shrinkage. By avoiding traditional co-stimulatory domains, the therapy maintains elevated cytokine levels for immune function without the extreme spikes seen in standard CAR-T designs. This milder profile could make future PSMA-CAR-T treatments safer for patients while remaining effective at killing tumor cells.​
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• B7-H3 Expression as a Prognostic Marker Across Disease Stages​
  A large observational study of over 8,000 prostate tumors has revealed that B7-H3 (CD276) expression serves as a prognostic marker whose meaning changes based on the disease stage. In primary and hormone-sensitive cases, high B7-H3 levels indicate worse overall survival, but in metastatic tumors, the same high expression is associated with better survival. Because B7-H3 levels remain stable across various disease states and correlate with other actionable antigens, it is a promising target for future therapies like antibody-drug conjugates and bispecific antibodies. The study also noted significant racial disparities in survival for Asian/Pacific Islander patients with metastatic disease regardless of B7-H3 levels.​
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• CEACAM5 Radiotheranostics for PSMA-Negative Neuroendocrine Prostate Cancer​
  For patients whose tumors have adapted to express low levels of PSMA or transitioned to neuroendocrine prostate cancer (NEPC), a new radiotheranostic strategy targeting the CEACAM5 antigen has emerged. This approach uses an imaging agent for PET scans followed by a therapeutic alpha-emitting agent, 225Ac-macropa-tusamitamab. Preclinical results were highly successful, with a single injection producing complete tumor responses in every treated animal by week three. This strategy offers a precision-targeted “rescue” option for the most drug-resistant phenotypes of prostate cancer.​
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• DNA Smart Drugs: A Double-Lock System for Precision Treatment​
  A new DNA-based drug system uses “logic gates” to ensure that powerful cancer drugs only activate when they identify a specific combination of two markers on a cell surface. This “double-lock” mechanism is designed to increase precision and protect healthy tissues that might only carry one of the markers at low levels. For prostate cancer, this platform could be adapted to target PSMA alongside a second marker, providing a more selective treatment for heterogeneous or treatment-resistant metastatic tumors. The system is highly flexible and could eventually carry various payloads, including toxic drugs or radiolabeled agents.​

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And…that’s all folks! For today at least!
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Have a great weekend!

Max