DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Combining Nanotechnology and Radiation to Enhance Checkpoint Blockade Immunotherapy of Advanced Prostate Cancer

Posted September 21, 2021

Wenbin Lin, Ph.D., University of Chicago
Ralph Weichselbaum, M.D., University of Chicago
Steven Chmura, Ph.D., University of Chicago

 Wenbin Lin, Ph.D., University of Chicago
Dr. Wenbin Lin

It is estimated that 1 in 7 men will be diagnosed with prostate cancer (PCa) in his lifetime. Although many men with PCa initially respond well to treatments including surgery, radiation, and/or hormone therapy, approximately 50,000 men a year experience recurrent, metastatic disease. Radiotherapy is a highly effective treatment option for visible tumors that can be directly targeted with X-rays, but is rarely sufficient in treating metastatic cancer cells that have spread throughout the body and often requires higher, toxic doses when treating recurrent disease. Research suggests that any benefit outside the direct site of the radiation is likely due to activation of the immune system, and this has been shown to be beneficial in other cancers through the successful combination of immunotherapy (via checkpoint blockade) with radiotherapy in treating both local and metastatic PCas. In an effort to develop new, less toxic and more effective radiotherapy-based treatments for recurrent and metastatic tumors, Drs. Wenbin Lin, Ralph Weichselbaum, and Steven Chmura at the University of Chicago are developing and testing new nanotechnologies to shrink local or metastatic prostate tumors with low X-ray doses while simultaneously boosting the patient’s own immune system to further enhance the response and fight metastasis.

Ralph Weichselbaum, M.D., University of Chicago
Dr. Ralph Weichselbaum

With funding from an FY17 Idea Development Award, the research team investigated the mechanism of an X-ray activated cancer vaccination process that combines cancer immunotherapies with a particular class of nanoparticles called nanoscale metal-organic frameworks (nMOFs). When activated by X-rays, nMOFs generate reactive oxygen species (free radicals) to kill tumor cells and release danger signals to the patient’s immune system. These danger signals help to educate and direct tumor specific immune cells to go out and kill metastases both within the prostate and throughout the body. Recently published results showed the potential of these nanoparticle/X-ray combinations to act as an in situ cancer vaccine (made in the body) to awaken the host’s immune systems for antitumor immunity. This technology can benefit PCa patients by enhancing the direct ability to kill local tumor cells while lowering the dose of radiation needed and thus decreasing toxicity.

 Steven Chmura, Ph.D., University of Chicago
Dr. Steven Chmura

This work demonstrates the potential of nMOFs as X-ray activated PCa vaccines and warrants the need for additional clinical studies. In the long term, the investigators hope this work will lead to new nanotherapeutics that can significantly improve the treatment outcomes of radiotherapy for patients with widely metastatic disease, and the benefits of an enhanced immune response may prolong survival and improve their quality of life.


Gann Murphy Figure
X-ray activated cancer vaccination by combining nMOFs and cancer immunotherapies. nMOF/CpG expands cytotoxic T cells to activate the adaptive immune system for tumor regression. (Adapted from Ni et al, Sci. Adv. 2020)

Publications:

Ni, K.; Lan, G, Guo, N.; Culbert, A.; Luo, T.; Wu, T.; Weichselbaum, R.R.; Lin, W. Nanoscale Metal-organic Frameworks for X-ray Activated in situ Cancer Vaccination. Sci. Adv. 2020, 6: eabb5223.

Ni, K.; Luo, T.; Culbert, A.; Kaufmann, M.; Jiang, X.; Lin, W. Nanoscale Metal-Organic Framework Co-delivers TLR-7 Agonists and Anti-CD47 Antibodies to Modulate Macrophages and Orchestrate Cancer Immunotherapy. J. Am. Chem. Soc. 2020, 142, 12579-12584.

Ni, K.; Luo, T.; Nash, G.; Lin, W. Nanoscale Metal-Organic Frameworks for Cancer Immunotherapy. Acc. Chem. Res. 2020, 53, 1739-1748.

Ni, K.; Lan, G.; Lin, W. Nanoscale Metal-Organic Frameworks Generate Reactive Oxygen Species for Cancer Therapy. ACS Cent. Sci. 2020, 6, 861-868.

Ni, K.; Lan, G.; Song, Y.; Hao, Z.; Lin, W. Biomimetic Nanoscale Metal-Organic Framework Harnesses Hypoxia for Effective Cancer Radiotherapy and Immunotherapy. Chem. Sci., 2020, 11, 7641-7653.

Link:

Combining Nanotechnology and Radiation to Enhance Checkpoint Blockade Immunotherapy of Advanced Prostate Cancer

Top of Page

Last updated Tuesday, September 21, 2021