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; however, they still rely on the activation of a faulty immune mechanism. CAR T cells, on the other hand, bypass immune-mediated activation and unleash the killing power of T cells once the programmed target cell has been found.
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.