Houston Methodist researcher receives $4 million to create triple negative breast cancer immunotherapy

Scientists at Houston Methodist received support from the U.S. Department of Defense (DoD) to reprogram cancer patients' immune cells to attack triple negative breast cancer, the most lethal form of breast cancer.

The DoD awarded Rongfu Wang, Ph.D., director of the Center for Inflammation & Epigenetics at Houston Methodist Research Institute, and Jenny C. Chang, M.D., director of the Houston Methodist Cancer Center, nearly $4 million to create a triple negative breast cancer immunotherapy that retrains the immune system to safely target and eliminate breast tumors and spare normal tissue.

The team removes immune cells from a triple negative breast cancer patient and isolates T cells, a small population of immune cells that help the body fight cancer and other diseases. Receptors of the tumor marker NY-ESO-1 are attached to the patient's T cells to recognize and capture cancer cells expressing the tumor marker. The modified NY-ESO-1 T cells are injected back into the patient as a personalized immunotherapy that guides the patient's immune system to identify and destroy breast cancer cells.

Wang led a team of researchers to identify the tumor marker NY-ESO-1, a protein found in only tumors and testes tissue. The absence of NY-ESO-1 from most normal tissues limits its side effects when used as an immunotherapy target. The DoD grant allows the Houston Methodist team to use NY-ESO-1 T cells to target triple negative breast cancer.

Recent clinical studies showed a 55 to 80 percent response rate of NY-ESO-1 T cells in treating patients diagnosed with metastatic synovial sarcoma, melanoma and myeloma, revealing NY-ESO-1 as an effective immunotherapy target for solid cancers. The highly specific tumor marker is expressed in 30 percent of tumors from triple negative breast cancer patients.

Breast cancer is the second leading cause of cancer death in women, according to the American Cancer Society. Ongoing research has kept survival rates at close to 100 percent in patients with early diagnosis of local disease. Rates plummet to a median of three years when the disease spreads to distant sites. Triple negative tumors lack the expression of three receptors: estrogen, progesterone and HER2, leaving most radiation and chemotherapies ineffective, toxic and ultimately resulting in disease relapse and death.
Wang, the lead investigator, and his team have studied the use of NY-ESO-1 in cancer vaccines and immunotherapy for nearly two decades.

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