UCSF Pilot Award to Help Develop Improved Method for 225Ac Radioimmunotherapy of Prostate Cancer

UCSF Pilot Award to Help Develop Improved Method for 225Ac Radioimmunotherapy of Prostate Cancer

Sep. 18, 2022, 6:00 a.m.

University of California's, San Francisco (UCSF) advanced targeted alpha therapy (TAT) agent called 225Ac-DOTA-YS5, can treat prostate cancer while allowing verification of its activity in prostate cancer models, according to Kondapa Naidu Boppa, Ph.D., assistant professional researcher in UCSF’s Department of Radiology and Biomedical Imaging. In the case of the UCSF advancement, the TAT uses radioimmunotherapy, helping to deliver high doses of highly lethal alpha participants to the targeted tumors. At UCSF, thus far, this particular agent has been used to target an antigen highly expressed in prostate cancer known as CD46. Now, UCSF researchers have received a pilot reward to develop further and improve the imaging and therapeutic agent targeting prostate cancer. Specifically, Kondapa Naidu Bobba, and Bin Liu, Ph.D., a professor in the UCSF Department of Anesthesia, secured a UCSF Resource Allocation Program (RAP) contribution: a “Pilot Award in Precision Imaging of Cancer and Therapy” for the formal study titled “Development of an improved method for 225Ac radioimmunotherapy of prostate cancer.”

What follows is a brief breakdown of this UCSF breakthrough.

This UCSF advancement falls into a category of imaging and therapeutic agents helping to better target and destroy tumors while minimizing the associated toxicity. For example, there is an emerging technology in which radiation is selectively targeted to tumors using molecular targeting radioligand therapy. This approach enables effective tumor treatment with minimal toxicity as compared to before.

TAT is an example of a highly targeted approach, delivering a highly lethal payload of alpha particles targeting tumors.

So what is 225Ac-DOTA-YS5 (YS5) developed at UCSF?

An imaging and therapeutic agent developed by UCSF investigators, specifically, it’s a targeted alpha therapy or “TAT” agent using radioimmunotherapy and is employed at high doses to zap tumors. With TAT, highly specific targeting immunoglobulins labeled with alpha emitters such as 225Ac are administered, which turn out to be effective for tumor control.

Is YS5 a clinical-stage agent?

Yes. The agent has been used in multiple clinical trials, such as NCT03575819 and NCT05011188 for mCRPC and  NCT03650491 for multiple myeloma.

Are there toxicity concerns?

Yes, because YS5 is a full-length human IgG1. Current YS5-based TAT agents have a long-circulating half-life, which may raise the concern of off-target toxicity.

What’s the UCSF position on minimizing potential toxicity?

In a recent entry from UCSF Radiology, increasing the ratio of tumor to normal tissue radiation delivery is a central goal for the development of radionuclide therapies to maximize therapeutic effect while minimizing toxicity.

What category does this UCSF breakthrough fall under?

This is an emerging technology in which radiation is selectively targeted to tumors using molecular targeting, enabling effective tumor treatment with minimal toxicity in many cases. Called Radioligand therapy, when paired with high-quality PET imaging agents utilizing the same targeting agent, this method allows physicians to "see what they treat" using the theranostic strategy.

UCSF has developed a TAT agent and again employs radioimmunotherapy to deliver high doses of the highly lethal alpha particles to the cancerous tumor target. In this case, immunoglobulins labeled with alpha emitters, in this example 225Ac, are administered, which further improves tumor control.

What will the internal UCSF grant help the investigators refine?

According to Dr. Bobba, the funding helps improve this agent with an aim of both maximizing therapeutic benefit while minimizing toxicity. One key area of importance, according to the co-principal investigator Dr. Bobba is the “use of novel linker technology to connect the therapeutic radioisotope 225Ac with highly specific targeting antibody YS5 for the treatment of prostate cancer.”

What is the unit in UCSF overseeing the research?

The grant-winning Dr. Bobba’s research is conducted in UCSF’s Radiology department’s Molecular Imaging Lab, also called the Flavell lab. This lab’s PI is Robert Flavell, MD, Ph.D., chief of Molecular Imaging & Therapeutics.

Members of this laboratory integrate new chemistry, chemical biology, imaging, and clinical methods with the aim of improving new methodologies to help advance patient care.

What other UCSF investigators received RAP funding?

Michael Evans, Ph.D. and Henry Vanbrocklin, Ph.D.

Lead Research/Investigator

Kondapa Naidu Boppa, Ph.D., assistant professional researcher in UCSF’s Department of Radiology and Biomedical Imaging.

Bin Liu, Ph.D., professor in the UCSF Department of Anesthesia.


 

Comments

Post a Comment

Popular posts from this blog

A 10-Second Steam Blast: The New Weapon Against Prostate Cancer?

Image
Vanquish® Water Vapor Ablation System, Francis Medical Steams Out Prostate Cancer The Vanquish® Water Vapor Ablation System, developed by Francis Medical, Inc. , represents an innovative approach to treating prostate cancer using water vapor (steam) to ablate cancerous tissue. This minimally invasive technique aims to target and destroy prostate cancer cells while minimizing damage to surrounding healthy tissue, potentially reducing common side effects associated with traditional treatments like surgery and radiation, Mechanism of Action:  The Vanquish system utilizes the thermal energy stored in sterile water vapor to ablate cancerous prostate tissue. During the procedure, a catheter is inserted through the urethra into the prostate, delivering water vapor directly to the targeted tissue. As the vapor condenses back into liquid, it releases stored thermal energy, effectively destroying the cancerous cells. This method is designed to respect the prostate's natural boundaries, ...
Read more

Researchers develop low-cost device that detects cancer in an hour | ScienceDaily

Image
Summary Sanjay S. Timilsina , currently Lead Scientist, StataDx, a spinoff from Wyss Institute, former Postdoctoral Fellow at Harvard Medical School and the Wyss Institute at Harvard University, PhD from UTEP Department of Chemistry & Biochemistry, and XiuJun Li full Professor in the Department of Chemistry and Biochemistry and of Forensic Science, & Environmental Science and Engineering, at the University of Texas at El Paso (UTEP) have developed a new portable device for cancer detection that offers several advantages over traditional methods: Key Features: - Low cost (a few dollars per device, <8 cents per assay) - Provides results in about 1 hour (vs. 12-16 hours for traditional methods) - Approximately 10 times more sensitive than traditional methods - Portable and doesn't require specialized instruments - Can detect both CEA colorectal and PSA prostate cancer biomarkers - Uses a "paper-in-polymer-pond" structure to analyze blood samples How it works: - U...
Read more

Cancer patients and doctors team up to change how cancer drugs are tested | Fox News

Cancer patients and doctors team up to change how cancer drugs are tested | Fox News foxnews.com Associated Press For cancer patients, the harsh side effects of powerful drugs have long been the trade-off for living longer. Now, patients and doctors are questioning whether all that suffering is necessary. They’ve ignited a movement to radically change how new cancer drugs are tested, with the U.S. Food and Drug Administration urging drugmakers to do a better job at finding the lowest effective dose, even if it takes more time. Advances in treatment mean millions of people are surviving for years with incurable cancers. Jill Feldman, 54, of Deerfield, Illinois, has lived 15 years with lung cancer , thanks to that progress. Her parents both died of lung cancer months after their diagnoses. But her cancer drug causes joint pain, fatigue and mouth sores that m...
Read more