DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS
  1. Home
  2. Research Programs
  3. Prostate Cancer
  4. Research Highlights
  5. 2015 Prostate Cancer Highlights
  6. Blocking T-Cell Co-Inhibitory Molecules to Improve Immune Response to Prostate Cancer
Blocking T-Cell Co-Inhibitory Molecules to Improve Immune Response to Prostate Cancer

Posted January 22, 2015
Xingxing Zang, M.Med, PhD, Albert Einstein College of Medicine of Yeshiva University

Xingxing Zang, M.Med, PhD The T cells of the body's immune system are major combatants against cancer; however, many tumors, including those from prostate cancer, have ways to block immune responses against them. Recently a new member of the B7 family of immune blockers, B7x, was discovered, and it was found that B7x, and its closest homolog B7-H3, were highly expressed by more than 90% of human prostate cancers. Patients with high expression levels of either molecule were significantly more likely to have their cancer spread, return back after treatment, and die at an earlier stage. These findings suggest that human prostate cancer cells may use B7x and B7-H3 to block the immune system, and drugs that counter their effects could be useful therapeutic agents.

With this in mind and with support from a 2009 PCRP New Investigator Award, Dr. Xingxing Zang, Ph.D, at the Albert Einstein College of Medicine of Yeshiva University, set out to elucidate the mechanisms which regulate immune responses, specifically those regarding B7x, and to translate that information towards the development of new therapeutic strategies for prostate cancer. During the investigation, Dr. Zang was able to show that prostate cancer cells expressing B7x displayed accelerated tumor progression in mouse in vivo model systems. Furthermore, the investigative team was able to develop several monoclonal antibodies (mAbs) that target B7x to reverse its effect. One of these mAbs, named 1H3, possesses dual activity by blocking B7x-mediated co-inhibition of the immune system's T-cell, and by producing a toxic effect in cells to directly initiate cell death in tumors.

Dr. Zang was also awarded a 2013 Idea Development Award to continue this line of work, and plans on translating the team's basic research finding to the clinical setting to move the results quickly into medical practice. Once humanized, the B7x targeting mAbs should be ready for clinical trials to assess their ability to reverse the co-inhibition of T-cells and allow the immune system to attack cancerous cells without damaging normal tissues. The Albert Einstein College of Medicine's Cancer Center has many project areas directly relevant to cancer immunology and provides a supportive infrastructure to help Dr. Zang move this PCRP-funded research closer to the clinic.

Figure from Dr. Zang

Publications:

Barach YS, Lee JS, Zang X "T cell coinhibition in prostate cancer: new immune evasion pathways and emerging therapeutics" Trends. Mol. Med. 2011 Jan; 17(1):47-55.

Jeon H, Vigdorovich V, Garrett-Thomson SC, Janakiram M, Ramagopal UA, Abadi YM, Lee JS, Scandiuzzi L, Ohaegbulam KC, Chinai JM, Zhao R, Yao Y, Mao Y, Sparano JA, Almo SC, Zang X "Structure and Cancer Immunotherapy of the B7 Family Member B7x" Cell Rep. 2014 Nov 6; 9(3); 1089-98.

Links:

Public and Technical Abstracts: Prostate Cancer-Associated T-Cell Coinhibitory Molecules: Potential New Tumor Evasion Pathways and Therapeutic Targets

Public and Technical Abstracts: Targeting B7x and B7-H3 as New Immunotherapies for Prostate Cancer

Top of Page