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Cancer Immunotherapy Adapted for HIV

T-cell infected by HIV

T-cell infected by HIV (NIAID, Flickr)

1 Feb. 2021. A biotechnology company is adapting and licensing its immunotherapy process, originally designed for cancer, as a cure for HIV infections. The deal with Gilead Sciences Inc. in Foster City, California could bring Gritstone Oncology Inc. in Emeryville, California as much as $785 million if all aspects the agreement are fulfilled.

Gilead Sciences develops and and now markets several drugs for treating HIV that suppress viral loads in people with the condition and prevent infections from advancing into Acquired Immune Deficiency Syndrome or AIDS. However, those drugs need to be taken regularly by people with HIV for the rest of their lives, often in combination with other drugs, to maintain their effectiveness.

Gilead says it wants a more durable treatment that destroys and not just suppresses HIV viruses, and is working with Gritstone Oncology on a solution.  Gritstone develops treatments for cancer and infectious diseases based on the specific DNA composition of target cells called neo-antigens. The company first created its technology, called Edge, for cancer to evaluate DNA from each patient’s tumor using genomic sequencing and bioinformatics to identify individual tumor-specific neo-antigens.

Gritstone then applies its own artificial intelligence algorithms to identify the most likely neo-antigens to activate an immune response, and delivers personalized synthetic neo-antigens for the patient as a vaccine, either on their own or with other therapies. Among Gritstone’s own treatments are T-cell receptors, naturally occurring proteins modified to target other characteristic proteins on the surface of target virus or cancer cells. As reported last month in Science & Enterprise, Gritstone is also applying its technology to a vaccine protecting against multiple Covid-19 viral variations.

Collaboration already underway

Gilead Sciences and Gritstone Oncology are collaborating on a treatment for HIV infections producing an immune-system response that destroys HIV viruses. Gritstone is developing the therapy with self-amplifying messenger RNA, or SAM, delivered with adenoviruses, benign viruses that are now workhorses for delivering gene and cell therapies. In the partnership, Gilead is providing HIV antigen targets.

“Curing HIV remains the ultimate aspiration for Gilead’s HIV research and development efforts,” says Diana Brainard, Gilead’s senior vice-president for virology therapeutics, in a statement. “Gritstone’s vaccine technology has the potential to educate the immune system to specifically recognize and destroy HIV-infected cells by leveraging SAM and adenoviral vectors.”

Gritstone already designed a prototype immunotherapy with an analog in monkeys similar to HIV known as simian immunodeficiency virus or SIV. Preclinical studies show the treatment invokes CD8+ T-cells, white blood cells in the immune system, that attack and eliminate the SIV viruses. “The resulting strong, durable and broad anti-SIV CD8+ T cell responses and T cell memory data captured the attention of Gilead’s virology team,” says Karin Jooss, Gritstone’s chief scientist. “We jointly performed further experiments that generated additional compelling data, which was also complemented by our exciting clinical data with neoantigens in cancer patients.”

The agreement gives Gilead Sciences an option to exclusively license Gritstone Oncology’s HIV immunotherapy candidate, following an early-stage clinical trial sponsored by Gilead. Should Gilead then acquire the rights to the immunotherapy, the company will be responsible for further development and commercialization. Gilead is providing a $30 million initial payment and taking a $30 million equity stake in Gritstone. In addition, Gritstone is eligible for $725 million in clinical, regulatory, and commercial milestone payments, and royalties on product sales, if all aspects of the deal are fulfilled.

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