Adeno-associated virus (AAV)-based gene therapy uses ‘gutted’ non-pathogenic viruses to carry good genes to cells to replace broken versions of the genes. However, normal immune responses to viruses limit gene therapies' use to a select number of patients.
Chameleon said its EVADER platform suppresses immune responses to gene therapies by leveraging molecules used by some tumor cells to evade immune detection and activation.
Therefore, the technology can help populations who presently cannot receive AAV gene therapies, it continued. Examples include children with fatal genetic diseases who need repeat doses of gene therapy because their organs are still growing, children and adults with prior exposure to AAV in their lifetimes, and gene therapy clinical trial participants who received an insufficient dose of gene therapy during their first treatment.
EVADER particles consist of a lipid membrane coated with immune suppressive proteins that deliver signals to allow gene therapies to get past the immune system. “By packaging AAV DNA carriers in protective lipid membranes, EVADER shields them from existing antibodies. Two naturally occurring human proteins attached to the lipid envelope also act as ‘checkpoint immune suppressors’ to prevent new antibody formation and T-cell activation.”
In animal models, the biotech said EVADER is proving to be very effective: not only does it overcome the immune response to AAV, but gene therapies that contain EVADER are more potent at delivering their transgene payloads.
Chameleon said the technology can be applied to any AAV.
"Having a scientific background in both gene therapy and immunology, I knew that bypassing the immune system would be crucial to bringing safer gene therapies to more patients," said Genine Winslow, founder and CEO of Chameleon Biosciences. "Chameleon's immunomodulatory solution uses a similar technique that some cancer cells use to evade detection. Our goal is to get lifesaving treatments to patients as many times as needed to reverse disease symptoms."
The founder has roots in immuno-oncology, linked back to James P Allison’s 2018 Nobel prize-winning work on checkpoint immune molecules, which resulted in the discovery that some cancer cells sneak past the human immune system by 'cloaking' themselves with harmless proteins, pretending to be healthy cells. Chameleon said EVADER allows treatment carrying AAV viruses to evade the human immune system in much the same way, minimizing immunogenic responses.