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Gene Therapy Could Revolutionize HIV Treatment


A gene therapy company in Tucson, Ariz. Is quietly but powerfully forging ahead on a small clinical trial that could revolutionize HIV treatment.

Calimmune Inc. in May obtained $15 million in financing “led by a large pharmaceutical company,” according to a news release, to keep its trial going. The trial is examining whether its treatment, a gene-based therapy called Cal-1, can control HIV infection with just one treatment.

Cal-1 works by reducing the expression of a protein on the surface of white blood cells, or T cells, called CCR5. HIV needs CCR5 to hone in on the cells and attack. Cal-1 also works by preventing the virus from entering white blood cells when it does find them.

In the clinical trial, four volunteers are being infused with their own blood stem cells, as well as mature T cells, that have been treated with Cal-1. Blood stem cells, also known as hematopoietic stem cells, can replicate into a variety of different cells, including the white blood cells used by the immune system.

“By reducing CCR5 expression and preventing HIV viral fusion, Cal-1 may protect the treated cells against HIV and has the potential to provide a continuous means of controlling HIV after a single treatment,” according to the news release.

The approach was shown to be effective in a test tube prior to clinical trials. Whether Cal-1 has proven effective in human clinical trials has yet to be announced. The therapy still is being assessed primarily for safety. A company spokesman told John Farrell, a writer for Forbes, that results may be disclosed prior to the conclusion of the trial in September. Farrell called Calimmune a company “definitely a company to keep an eye on in 2016.”

Strategies targeting CCR5 in immune therapy have flourished after Timothy Ray Brown, also known as “The Berlin Patient,” became the first person on earth ever to be functionally cured of HIV. Brown had acute myeloid leukemia as well as HIV. His leukemia was cured after receiving an allogenic stem cell transplant from a donor with a CCR5 delta 32 mutation. People who are homozygous (meaning the same two alleles on a gene) for CCR5 delta 32 are resistant to HIV.

“The next logical step in the evolution of HIV/AIDS patient care is finding a cure by enhancing the body’s own defenses,” said Louis Breton, chief executive officer of Calimmune.

It all sounds great, but will it really work?

The Timothy Ray Brown case has yet to be replicated. In other people where doctors have been hopeful for a cure after stem cell transplants, the virus, which hides in latent reservoirs, roars back after antiretroviral therapy is stopped.

In a letter published in 2014 in the New England Journal of Medicine, Dr. Lambros Kordelas et al. described the case study of a patient with T-cell lymphoma and HIV who also was given a stem cell transplant from a homozygous CCR5 delta 32 donor.

Their analysis showed that after the patient was given the stem cell transplant, the HIV in his body shifted its mode of attack from entry via the CCR5 receptor to entry via the CXCR4 receptor. The patient eventually died. Viral load was 7,582,496 copies per milliliter two weeks before death.

“The genotypic analyses of HIV-1 variants in this patient showed a shift from a dominantly R5-tropic HIV before stem-cell transplantation toward an X4-tropic HIV after transplantation,” the authors reported. “This shift of tropism was probably driven by transplantation with stem cells homozygous for the CCR5 delta32 mutation. This case highlights the fact that viral escape mechanisms might jeopardize CCR5-knockout strategies to control HIV infection.”

In June of 2014, Calimmune announced in a news release that after an initial trial involving four HIV-positive patients a Data Safety Monitoring Board concluded that Cal-1 was safe. “The DSMB confirmed that none of the participants experienced any serious adverse events or dangerous side effects from the therapy.”

The safety declaration allowed Calimmune to begin treating the second cohort of patients who not only received Cal-1 but also a “preconditioning regimen with the aim of making the therapy more effective,” Calimmune reported.

“With more than one million Americans living with HIV, there is clearly an urgent need for a therapy that does more than just hold the virus at bay,” said Jonathan Thomas, chair of the stem cell agency’s governing board. “Current medications are effective, but come with a big cost both in terms of dollars and side effects. Our goal is to find an approach that effective cures people with HIV/AIDS.”

The Calimmune trials are being conducted at Quest Clinical Research in San Francisco and the UCLA Care Center in Los Angeles. “Calimmune has assembled a world-class team and a comprehensive technology arsenal that harnesses the power of gene therapy to combat HIV and potentially a wide range of challenging diseases,” said Peter Kolchinsky, a managing partner at RA Capital, a Calimmune investor.