Chimeric antigen receptors are genetically modified T-cells, created by engineering a patient’s own immune cells so they can seek out and bind to cancer cells and kill them. CAR T-cell immune therapy has proven successful for some blood cancers but solid tumors present additional challenges.
Now an oncologist at Baylor College of Medicine is exploring ways of engineering T-cells to successfully attack solid tumors like breast cancer. Physician-scientist Dr. Valentina Hoyos Velez, M.D., was recruited in 2017 from Johns Hopkins University where she was a clinical fellow in hematology and oncology. She previously was a resident at Baylor and received a First-Time Tenure-Track Award from CPRIT to facilitate her return to Texas.
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Chimeric antigen receptors are genetically modified T-cells, created by engineering a patient’s own immune cells so they can seek out and bind to cancer cells and kill them. CAR T-cell immune therapy has proven successful for some blood cancers but solid tumors present additional challenges.
Now an oncologist at Baylor College of Medicine is exploring ways of engineering T-cells to successfully attack solid tumors like breast cancer. Physician-scientist Dr. Valentina Hoyos Velez, M.D., was recruited in 2017 from Johns Hopkins University where she was a clinical fellow in hematology and oncology. She previously was a resident at Baylor and received a First-Time Tenure-Track Award from CPRIT to facilitate her return to Texas.
Solid tumors present several obstacles to CAR T-cell immune therapy that blood cancers do not. Perhaps the most serious one is that these tumors are already infiltrated with immune cells that have had their tumor-killing abilities switched off by the tumor.
Tumors are inherently inflammatory, recruiting immune cells from a patient’s bone marrow. But when these immune cells arrive, they become disabled by the tumor and no longer attack the enemy they came to slay. Instead, these cells become corrupt, and the immune army helps defend the enemy, the tumor, instead of killing it.
Dr. Hoyos Velez is engineering CAR T-cells that have both the ability to bind to breast cancer cells and also contain a trigger switch that can stimulate these corrupt immune cells to commit suicide in a sort of cellular harikari.
She’s currently testing her engineered T-cells in mouse models of breast tumors. The next step is to engineer T-cells directly derived from patients with breast cancer and test their anti-tumor activity. The Lester and Sue Smith Breast Center at Baylor maintains a library of tumors derived from patients, but unfortunately, not blood from the same patients. Dr. Hoyos Velez needs blood matched to the tumor to create her modified T-cells. To accomplish this, she’s collecting blood from patients who have survived and will eventually use these samples to engineer personalized T-cells to attack patient-derived tumors grown in mice.
Dr. Hoyos Velez hopes to move to a clinical trial in patients within a few years. Eventually, she believes, the future of T-cell immune therapy will be off-the-shelf products derived from healthy donors.
Dr. Hoyos Velez maintains a clinical practice seeing breast cancer patients because she says it helps her to understand cancer from the patient’s perspective.
CPRIT support enabled her to hire people and get her lab up and running — essentially instead “of taking baby steps, I’ve started out running,” she says. The CPRIT investment has already leveraged two other grants, including a prestigious career-catalyst award from the Susan G. Komen foundation.
Dr. Hoyos Velez received her medical training at Pontificia Universidad Javeriana in Bogotá, Colombia. She first came to Baylor in 2006 as a research intern, planning to stay only six months. But she ended up remaining as a clinical and research fellow and after six years, completed her residency in internal medicine. She began her clinical fellowship at Johns Hopkins in 2014.
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