This week, UCLA scientist Scott Kitchen made the news for his efforts to develop a CIRM-funded stem cell gene therapy that could potentially cure patients infected with HIV. Kitchen’s work was profiled in the Daily Beast, which argued that his “research could significantly up survival rates from the virus.”
Kitchen and a team of scientists at the UCLA David Geffen School of Medicine are genetically modifying blood-forming, hematopoietic stem cells (HSCs) to express chimeric antigen receptors (CARs) that target HIV-infected cells. CARs are protein complexes on the surface of cells that are designed to recognize specific types of cells and are being developed as powerful immunotherapies to fight cancer and HIV infection.
These CAR-expressing HSCs can be transplanted into patients where they develop into immune cells called T cells and natural killer (NK) cells that will destroy cells harboring HIV. This strategy also aims to make patients resistant to HIV because the engineered immune cells will stick around to prevent further HIV infection.
By engineering a patient’s own blood-forming stem cells to produce an unlimited supply of HIV-resistant immune cells that can also eradicate HIV in other cells, Kitchen and his team are creating the possibility for a life-long, functional cure.
Dr. Kelly Shepard, Senior Science Officer of Discovery and Translation Research at CIRM, reflected on significance of Kitchen’s research in an interview:
“This unique approach represents a two-pronged strategy whereby a patient’s own stem cells are engineered not only to be protected from new HIV infection, but also to produce HIV-specific CAR T cells that will seek out and destroy existing and new pools of HIV infection in that patient, ideally leading to a lifelong cure.”
Kitchen and his team are currently testing this stem cell-based CAR-T therapy against HIV in a large-animal model. Their latest findings, which were published recently in the journal PLOS Pathogens, showed that stem cell-derived human CAR T cells were effective at reducing the amount of HIV virus (called the viral load) in their animal-model. They also saw that the CAR T cells survived for more than two years without causing any toxic side effects. This work was funded by an earlier CIRM award led by another CIRM grantee, Dr. Jerome Zack, who is research collaborator of Kitchen’s.
In December 2017, Kitchen received a $1.7 million CIRM Discovery Stage Quest award so that the team can continue to optimize their stem cell CAR T therapy in animal models. Ultimately, they hope to gain insights into how this treatment could be further developed to treat patients with HIV.
Currently, there is no widely available cure for HIV and standard antiretroviral therapies are expensive, difficult for patients to manage and have serious side effects that reduce life expectancy. CIRM has awarded almost $75 million in funding to California scientists focused on developing novel stem cell-based therapies for HIV to address this unmet medical need. Three of these awards support early stage clinical trials, while the rest support earlier stage research projects like Kitchen’s.
CIRM Communications Director, Kevin McCormack, was quoted at the end Daily Beast article explaining CIRM’s strategy for tackling HIV:
“There are a lot of researchers working on developing stem cell therapies for HIV. We fund different approaches because at this stage we don’t know which approach will be most effective, and it may turn out that it’s ultimately a combination of these approaches, or others, that works.”