LAST WEEK TODAY!

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

Hi fellow warriors! We have 3 clinical and 3 preclinical research today, but since the second half of August is always a bit “slow,” so I took the opportunity to create an article of my own that tries to summarize almost a year of articles published on ProstateWarriors.com (it will be one year in November). It’s a very long article, even though only a few lines are dedicated to each new piece of research or drug. You can save it and use it as a list if you wish. I couldn’t publish it within the Newsletter due to space limitations, but you can access it by clicking here. 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 2 Trial of 2141-V11: A New Immunotherapy Showing Systemic Remission​
  An investigational immunotherapy drug, 2141-V11, has demonstrated remarkable success in a Phase 1 clinical trial, leading to complete remission in some patients with aggressive metastatic cancers, including melanoma and breast cancer. Developed by Rockefeller University, this enhanced CD40 agonist antibody overcomes the significant toxicity and limited efficacy of previous drugs in its class by being ten times more powerful in eliciting an antitumor immune response. Crucially, its administration via direct injection into tumors drastically reduced systemic side effects. The drug’s effect was not limited to the injected tumors, as distant tumors also shrank or disappeared, indicating a powerful systemic response. These findings have initiated further clinical trials, including studies for prostate cancer, bladder cancer, and glioblastoma, with nearly 200 patients currently enrolled across these studies.
  ​
• Phase 1/2 Trial of HLD-0915: Fast Track for a Novel Cancer-Targeting Therapy​
  HLD-0915, an orally administered, investigational therapy, has received Fast Track Designation from the U.S. Food and Drug Administration (FDA), which is expected to accelerate its review and approval process. This bifunctional small molecule therapy operates as a RIPTAC, a novel class of molecules designed to selectively target cancer cells. Its unique mechanism involves inducing proximity between a tumor-specific protein and an essential effector protein, specifically binding to the androgen receptor (AR). This innovative approach offers a new, oral, and selective cancer cell-killing mechanism with the potential to overcome drug resistance, making it applicable for both advanced cases where resistance has emerged and in early-stage disease.
  ​
• Phase 1/2 Trial of Intermittent Fasting: A Potential Adjuvant for Prostate Cancer Therapy​
  A preclinical study published in Cancer Research on August 8 has revealed that intermittent fasting substantially increases the efficacy of anti-androgen therapy in prostate cancer animal models. This research demonstrated for the first time that this dietary approach enhances the effectiveness of enzalutamide, an androgen receptor inhibitor commonly used in prostate cancer therapy. In multiple mouse models of prostate cancer, alternate-day fasting led to a reduction in androgen receptor expression and signaling, and decreased amino acid levels and global protein synthesis within prostate cancer tumors, thereby making them more sensitive to the drug and enhancing its antitumor activity. These findings suggest that dietary interventions could become a vital “adjuvant tool” in cancer treatment. Building on these encouraging preclinical results, the University of Buffalo is actively recruiting patients for clinical trials on restricted eating in prostate cancer patients receiving hormone therapy.

​
Preclinical Research

• Promising Preclinical Research: A New Genetic Engineering Tool Revolutionizing Cancer Research​
  Chinese scientists have developed a programmable chromosome engineering tool capable of precisely editing millions of DNA bases, representing a significant leap in genetic engineering. Building on earlier methods like CRISPR/Cas9, TALENs, and Zinc Finger Nucleases, this technology allows for extensive and highly accurate chromosomal changes, including targeted insertion, replacement, inversion, deletion, and even chromosome translocations on DNA fragments ranging from thousands to millions of base pairs. In cancer research and treatment, this tool opens promising avenues for correcting cancer-driving mutations in genes like TP53 and KRAS, and for engineering immune cells (e.g., genetically modifying T cells to better recognize and destroy cancer cells, enhancing CAR-T effectiveness, and disrupting genes like PD-1). It also enables researchers to create synthetic cancer models that more closely mimic tumor genomes, accelerating the study of cancer progression and drug responses. Furthermore, it supports a new era of personalized medicine by allowing precise edits tailored to an individual’s unique tumor mutations. Beyond cancer, it has already shown practical applications by being used to create herbicide-resistant rice.
  ​
• APVO442: A Preclinical Bispecific Antibody for Prostate Cancer​
  Seattle-based biotech is advancing APVO442, a promising preclinical bispecific antibody designed to transform prostate cancer treatment by unleashing the body’s immune system against tumors with greater precision and fewer side effects. APVO442 is designed to target prostate-specific membrane antigen (PSMA) on prostate cancer cells while simultaneously engaging CD3 on T cells to direct immune attacks specifically at tumors. Preclinical animal model studies revealed significant tumor reduction in PSMA-positive prostate tumors, driven by potent T-cell redirection and cytotoxicity, with minimal impact on healthy tissues and no cytokine release syndrome observed in preclinical settings. Early human trials of mipletamig, another clinical-stage candidate using the CRIS-7 domain for acute myeloid leukemia (AML), achieved an impressive 85% remission rate.
  ​
• KCL-HO-1i: Targeting the Immunosuppressive Tumor Microenvironment​
  KCL-HO-1i is a novel, orally bioavailable small-molecule inhibitor targeting heme oxygenase-1 (HO-1), an enzyme that plays a key role in sustaining immunosuppressive tumor microenvironments by modulating a subset of perivascular tumor-associated macrophages (PvTAMs). While primarily studied in preclinical models of breast cancer and sarcoma, its mechanism of disrupting HO-1 activity to convert an immunologically “cold” tumor microenvironment into a “hot” one, characterized by increased infiltration of effector CD8+ T cells and enhanced chemotherapy efficacy, makes it highly relevant to prostate cancer. Prostate cancer shares features with these models, notably the presence of immunosuppressive tumor-associated macrophages (TAMs) that promote tumor progression, metastasis, and resistance to therapies. By inhibiting HO-1 in these macrophages, KCL-HO-1i could potentially reprogram the prostate tumor microenvironment, enhancing immune-mediated tumor control and improving the effectiveness of existing treatments such as chemotherapy or immunotherapy.
  ​
  ​

And…that’s all folks! For today at least!
Please let me know if there is anything I can improve in my newsletters, and let me know if you have enjoyed the podcast.

If you this newsletter was delivered to your SPAM folder, make sure to let your email system know that it is not spam.
​
​
Have a great weekend!

Max