A Pilot Award to Development an Improved Method for 225Ac Radioimmunotherapy of Prostate Cancer
Radioligand therapy 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. 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.
In particular, targeted alpha therapy (TAT) using radioimmunotherapy may be employed to deliver very high doses of highly lethal alpha particles to tumors. In this method, highly specific targeting immunoglobulins labeled with alpha emitters such as 225Ac are administered, which are highly effective for tumor control.
"At UCSF Radiology, we have developed a highly effective TAT agent, 225Ac-DOTA-YS5, for the treatment of prostate cancer, and verified its activity in prostate cancer models," says Kondapa Naidu Bobba, PhD, assistant professional researcher in the UC San Francisco Department of Radiology and Biomedical Imaging. "This agent targets CD46, an antigen that is highly expressed in prostate cancer, among other malignancies."
YS5 is a clinical stage antibody that was developed by UCSF investigators and brought to multiple clinical trials (NCT03575819 and NCT05011188 for mCRPC, and NCT03650491 for multiple myeloma). However, 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. 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.
Dr. Bobba is one of eleven researchers awarded grants in support of cancer research projects in the spring 2022 cycle of the UCSF Resource Allocation Program (RAP). These awards are funded by agencies across UCSF and span a range of topics. Dr. Bobba's Pilot Award in Precision Imaging of Cancer and Therapy is for his project on "Development of an improved method for 225Ac radioimmunotherapy of prostate cancer." He will be the principal investigator (PI) on the grant, along with co-PI Bin Liu, PhD, a professor in the UCSF Department of Anesthesia.
"The most exciting part of this research is the use of novel linker technology to connect the therapeutic radioisotope 225Ac with the highly specific targeting antibody YS5 for the treatment of prostate cancer," says Dr. Bobba. "This strategy will maximize the therapeutic benefit and minimize toxicity."
Dr. Bobba performs research in the Molecular Imaging Lab at UCSF Radiology. Robert Flavell, MD, PhD, chief of Molecular Imaging & Therapeutics, is the lab's PI. Members of the laboratory integrate new chemistry, chemical biology, imaging, and clinical methods, with the goal of developing new methodologies to help improve patient care.
Congratulations to Dr. Bobba and other UCSF Radiology investigators who received RAP funding – Michael Evans, PhD and Henry Vanbrocklin, PhD.