LAST WEEK TODAY!

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

Hello fellow warriors! Here we are again, with more news about the new weapons that are being developed. 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: Boosting Sipuleucel‑T with the IL-15 Superagonist N‑803​
  A Phase Ib clinical trial at Washington University is evaluating whether combining the cellular immunotherapy sipuleucel‑T with the IL‑15 receptor superagonist N‑803 (Anktiva) can generate a stronger immune response in patients with metastatic castration‑resistant prostate cancer (mCRPC). Sipuleucel‑T works by priming a patient’s antigen-presenting cells against prostatic acid phosphatase (PAP) to teach the immune system to recognize the cancer, while N‑803 is engineered to expand and sustain the cytotoxic CD8⁺ T cells and NK cells needed to carry out those instructions. In the past, sipuleucel‑T alone demonstrated a modest overall-survival benefit of 4.1 months in the IMPACT trial, typically without causing rapid PSA declines or tumor shrinkage. Investigators hope that adding N‑803 will provide the necessary cytokine “fuel” to expand these primed T cells, potentially converting sipuleucel‑T’s historical survival signal into deeper clinical responses and prolonged disease control.
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• Phase 1 Trial: PGV001 Personalized Therapeutic Vaccine with CDX-301​
  Mount Sinai is conducting a Phase 1 clinical trial evaluating PGV001, a personalized therapeutic peptide vaccine designed to target residual cancer cells, in combination with the immune-strengthening cytokine CDX-301. Unlike preventive vaccines, this therapeutic vaccine is created by sequencing each patient’s blood and tumor tissue to identify unique, patient-specific mutations.Mutation-derived peptides are then selected and synthesized to match the patient’s MHC molecules to effectively stimulate T cells. The trial is enrolling patients who have completed surgery and standard treatments and have no clinically detectable tumors, but remain at a high risk of recurrence, defined by a persistent or recurrent PSA of at least 0.2 ng/ml or a 30% or greater five-year biochemical-recurrence risk.​
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• Phase 1/2 Trial: CRISPR-Edited Treg Cell Therapy CRG-150​
  A first-in-human Phase 1/2a clinical trial is assessing CRG-150, an autologous, CRISPR-edited cell therapy, for heavily pretreated patients with relapsed or refractory metastatic prostate cancer and other solid tumors. The therapy targets and disrupts steroid receptor coactivator 3 (SRC-3) in regulatory T cells (Tregs), which typically suppress antitumor immunity in the tumor microenvironment. By disabling SRC-3, CRG-150 aims to reprogram these cells to stimulate a robust local antitumor immune response rather than blocking it. A major differentiator of this study is the planned absence of lymphodepleting chemotherapy before the patient receives the infusion. Rather than looking strictly for rapid PSA declines or tumor shrinkage, investigators will prioritize verifying that CRG-150 successfully survives in patients, home in on tumors, and successfully alters local immune-cell activity.​
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• Phase 2 Trial: Long-Term Overall Survival with pTVG-HP DNA Vaccine​
  Long-term follow-up from a randomized Phase 2 trial suggests that the DNA vaccine pTVG-HP (MVI-816) may significantly extend overall survival in men with PSA-recurrent, non-metastatic, castration-sensitive prostate cancer. The trial enrolled 99 men who had a PSA doubling time of under 12 months but no conventional radiographic metastases, comparing two years of treatment with pTVG-HP (which encodes PAP) plus GM-CSF against GM-CSF alone. Although the vaccine failed to meet its primary endpoint of 2-year metastasis-free survival (which was nearly identical between both arms), a late overall survival analysis showed a median survival of 13.4 years in the vaccine arm compared to 8.6 years in the control group, representing a 58% relative reduction in mortality risk. These exploratory findings match similar survival-disconnect phenomena seen with sipuleucel-T, though a larger prospectively powered trial with contemporary therapy is needed to confirm the true vaccine effect.​
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Preclinical Research & Reviews

• How Prostate Cancer Rewires Amino Acid Metabolism to Resist Therapy​
  A preclinical study from Weill Cornell Medicine published in Nature Metabolism reveals that prostate cancer cells can bypass hormone therapies by altering how they use common dietary nutrients. The research shows that tumors hijack the metabolism of two common amino acids, isoleucine and valineto produce a small molecule called propionyl‑CoA. Propionyl-CoA chemically modifies the cholesterol-regulating protein SREBP2, locking it in the “on” position so that the cell continuously synthesizes cholesterol regardless of actual levels. This unchecked cholesterol is then converted locally into androgens, which reactivates the androgen receptor pathway and blunts the effectiveness of therapies like enzalutamide.​
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• SCD1 Inhibition Combined with Enzalutamide to Overcome Lipid Escape​
  Preclinical research shows that combining an inhibitor of the enzyme SCD1 with enzalutamide may block a key metabolic escape route used by resistant prostate cancer cells. SCD1 helps cancer cells convert saturated fatty acids into monounsaturated fatty acids to support survival signaling, energy storage, and cell membrane integrity. While enzalutamide suppresses the hormonal growth signals of the androgen receptor, cancer cells frequently adapt by altering their lipid metabolism and relying on fatty-acid desaturation. Inhibiting SCD1 at the same time deprives the tumor of the lipids it needs to maintain these survival mechanisms. Preclinical testing of the SCD1 inhibitor Aramchol (an agent already in Phase 3 trials for NASH) combined with enzalutamide produced a 3- to 4-fold increase in cell death compared to enzalutamide alone in patient-derived VCaP cells that express advanced, treatment-resistant genetic features.

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

Max