| March 6
March 6 Treating HIV patients first with a
chemotherapy drug improved their response to an experimental
gene-modifying technique for fighting the virus, according to
The company presented data from an early-stage trial of its
treatment, SB-728-T, on Thursday at the Conference on
Retroviruses and Opportunistic Infections in Boston.
Late on Wednesday, data from an earlier trial showed that
Sangamo's strategy of genetically modifying cells from people
infected with HIV could become a way to control the virus that
causes AIDS without using antiviral drugs.
The technique is designed to disrupt a gene, CCR5, used by
human immunodeficiency virus to infect T-cells, the white blood
cells that fight viral infections. A patient's cells are removed
and processed to alter the DNA that codes for the CCR5 receptor.
The altered cells are multiplied and tested, then infused back
into the patient.
The results presented on Thursday show that increasing doses
of the chemotherapy drug Cytoxan, or cyclophosphamide, before
infusion with SB-728-T led to an improvement in both growth of
the genetically modified cells and an increase in total CD4
immune system cells, which otherwise would be a target for HIV,
according to Sangamo.
Two of three patients treated with the highest Cytoxan dose
have remained off of antiretroviral drugs for several weeks with
detectable, but stable, levels of HIV in their blood, the
company said. In all, nine patients received Cytoxan to augment
Cytoxan, made by Bristol-Myers Squibb, is used to
reduce the number of T-cells in the body, which then rapidly
repopulate once the drug is discontinued. The aim is to allow
SB-728-T to be infused as new T-cells are growing in the body.
Cytoxan is generally used to enhance effectiveness of bone
marrow transplants in cancer patients and as therapy for
The gene editing technique behind SB-728-T seeks to mimic
the resistance to HIV observed in the small number of people who
have inherited CCR5 mutations from both parents.
Sangamo has also been carrying out clinical studies in HIV
patients who have one copy of the natural mutation.
So far, the company has used a deactivated virus to deliver
its gene-modifying technology to patients, but said it will
shift to a new method using messenger RNA to deliver the
cell-altering proteins. Messenger RNA is a single-strand
molecule that carries information telling cells which proteins
When a virus is used to deliver gene therapy, patients
develop antibodies, making them immune to further treatments. By
using messenger RNA, patients can be re-treated with SB-728-T if
needed, said Sangamo spokeswoman Elizabeth Wolffe.
Sangamo said it has expanded the Cytoxan preconditioning
study to determine the right dose of the chemotherapy. It then
plans to treat an additional 12 subjects, using the new
messenger RNA delivery method, this year.
"If those data are positive, plans are to move forward with
pivotal trials with a pharma partner," said Sangamo Chief
Executive Officer Edward Lanphier, referring to efforts to sign
on a bigger drugmaker to help with funding. He did not give
details on whom Sangamo might approach.
Sangamo is testing its "gene editing" strategy to develop
therapies for a number of diseases, including inherited
illnesses such as hemophilia, sickle cell disease and