If you had asked me 6 years ago about using gene therapy to fight HIV/AIDS, I would have given you a nice rant about how expensive it is, how non-viable it is in the places that need anti-HIV strategies the most, how dangerous it can be, and I would have been damn offended you even considered it. Waste of valuable resources.
Flash forward to today… I am actually starting to think its not such a bad idea.
Well, specific kinds of gene therapy for HIV-1 might not be such a bad idea. One such idea is ‘Chimeric Antigen Receptors‘, or, CARs. CARs are half laboratory designed antibody (to recognize EXACTLY what your target is), half laboratory designed T-cell receptor signalling domains (designed to be really, REALLY good at killing targets).
When a Cytotoxic T-cell is forced to express a CAR, it should turn into a killing machine– seek and destroy whatever the antibody is designed to recognize.
In the case of HIV-1, this is actually a pretty good idea. Yes, you could also do gene therapy to force B-cells to make broadly neutralizing antibodies… but to get the virus you would have to have the right antibody at the right place at the right time in the right concentration. And then, you are targeting virus. Billions upon billions of targets.
Gene therapy strategies that utilize CARs would be a little different– instead of going after the virus, it goes after the infected cells. The producers of virus. Its like, instead of blowing up fighter jets (what antibodies do), CARs blow up the battleship launching the fighter jets.
Seems like a great idea! But things that look like great ideas can turn into huge freaking trainwrecks, and nowhere is this more apparent than with gene therapy trials.
But a group of folks have tried a CAR approach with HIV-1. They tried it 10 years ago. And their patients are still doing okay:
They made a CAR that had an outside bit that looked like CD4 (the receptor HIV-1 needs to infect cells) and an inside part that told the infected cells to die– Thus when a Cytotoxic T-cell expressing one of these CARs rolled by an HIV-1 infected cell, its ‘pseudo CD4′ would interact with the Envelope present on the surface of the infected cell, then the CTL ‘persuaded the infected cell to commit suicide. This was all accomplished via a retroviral gene therapy vector (DANGER! DANGER WILL ROBINSON!)
No, not ‘DANGER!’ A lot have things have changed since those first gene therapy trials.
Whether the experimental strategy actually worked to treat the individuals HIV-1, I dont know. But the paper they just published demonstrated that the approach they used is safe. If the approach is safe, then we can always fine tune what the CAR recognizes on the outside. We can always fine tune the CTL activation signals that go on in the inside.
The approach used to seem ‘absurd’, but if it works, if we can find an ‘absurd’ approach that works… we can work with that. Eliminating HIV-1 might require a lot of ‘absurd’ ideas being implemented…