Using Groundbreaking CAR-T Cancer Therapy to Eliminate HIV
Jeffrey Laurence, M.D.
Dr. Scott KitchenOn August 30, 2017, the U.S. Food and Drug Administration approved Kymriah as the first gene therapy for patients with a drug-resistant form of acute leukemia. The chimeric antigen receptor (CAR) therapy involves modifying a patient’s own T cells to seek and destroy cancer cells. It is a one-time treatment, and for many people, a lifesaving one. The approval of this therapy received worldwide publicity. But what may come as a surprise to many is the critical role HIV research played in the development of Kymriah, and how this proof-of-concept treatment for cancer relates to progress toward an HIV cure.
Writing in the September issue of the journal Translational Research, amfAR-funded scientist Dr. Scott Kitchen and colleagues from the University of California, Los Angeles note that most investigators believe that enhancing a person’s natural immune response will be key in eliminating HIV-infected cells. Indeed, HIV-specific CD8+ killer T cells can be engineered to inhibit HIV growth and reduce the size of the HIV reservoir in the test tube. But this strategy has numerous drawbacks, including the need to alter HIV killer cells based on an individual’s HLA tissue type. CARs are based on engineering CD4+ T cells, which don’t have that requirement. Almost all HIV-infected patients can be treated with the therapy, regardless of genetic makeup.
The researchers explain that the first CAR T cells to be used in clinical trials were actually designed and tested for the treatment of HIV—not cancer. In addition, in order to enable those cells to recognize infected cells, a self-inactivating lentivirus—a modified form of HIV—was used to introduce the necessary genes. However, pilot trials showed less than satisfactory results, as unlike cancer, HIV can attack the very CAR T cells administered to fight the infection. With this in mind, Kitchen and associates discuss several novel approaches to enhance the activity of anti-HIV CAR T cells and to protect them against infection.
These strategies include removing, through genetic engineering, the primary HIV co-receptor CCR5. (The “Berlin patient” became the first person to be cured of HIV after receiving a stem cell transplant from a donor with a CCR5 mutation.) The scientists also propose a combination approach to kill infected cells and eliminate latent HIV reservoirs.
The authors conclude: “CAR-based therapy for HIV infection is becoming a promising approach to provide lifelong immune surveillance and viral suppression without the use of antiretroviral therapy … a closer step toward a functional cure for HIV.”
Dr. Laurence is amfAR’s senior scientific consultant.