This study is a case study from this study (lol):
I imagined this scene happened in one of their lab meetings:
I didnt go in-depth as to how everything was working before, so I thought I would do it now!
This paper is a case report of an individual who had a B-cell cancer. The patient had tried everything and anything recommended to him by scientists (no mention in the report of him disappearing for 6 months to Mexico for ‘vitamin c’ therapy, or whatever stupid thing wooers push to ‘cure’ cancer) and he was still dying. Fast.
So he agreed to an experimental procedure designed by scientists.
Fact #1– B-cells and especially B-cell lymphomas express a protein, CD19.
Humans will not have antibodies to human CD19 (your immune system normally has ways of protecting itself from autoimmunity), but its really easy to get mice to make anti-human-CD19 antibodies.
Theoretically, these antibodies could be humanized (humans dont like mouse antibodies), produced industrially, and infused into cancer patients as a treatment, as the antibodies would tag the cancer for destruction.
In fact, that is exactly what a drug, Rituximab, does (it targets a different protein, though). And, unfortunately, this patient tried that, and it didnt work.
Fact #2– T-cells could also be used to kill cancers (technically, ‘persuade the cancer to commit suicide’).
T-cells have receptors on their surface that ‘read’ the proteins presented in cells MHC molecules. Normally, if a cell is infected with say, a virus, the cell will put up ‘VIRUS’ flags on their MHC molecules, and a T-cell will cruise by and say ‘Hey… that aint right…’ and kill the virally infected cell (MHC posts on ERV).
The problem is, cancers are basically *you*, just you gone wrong. And again, your immune system has ways of preventing autoimmunity. And, everyones MHC proteins are different– even if we could theoretically get your T-cells to attack cells making CD19, the flag my cells put up in my MHC would be different than yours. Treating a cancer this way would have to be super personalized based on individuals genetic profiles. HUGE pain in the butt, if not unwieldy to the point of being impossible except for the most common MHC types.
Solution– Combine Fact #1 and Fact #2 into one treatment.
Scientists in this study took the ‘arms’ off of mouse anti-CD19 antibodies (F(ab)2), and attached them to signaling domains normally found around the T-cell receptors (CD3 and a CD137 just to make the signal stronger).
So a T-cell expressing this protein would have the arms on an anti-B-cell-cancer on the outside, with the super powerful ‘KILL THIS CELL!!’ signaling domain on the inside. If the outside comes into contact with a cancer cell, the T-cell will kill it, and we wont have to deal with any of the issues of ‘my MHC is different than your MHC’!
But how the hell are you supposed to get a T-cell to express this kind of thing? Half antibody/Half TCR isnt normal at ALL. Well, they took the genetic information required to make this chimera (half super-specific anti-cancer antibody, half super powerful anti-cancer signaling domain) and put it into HIV-1. Well, a gutted out HIV-1 that can only reverse transcribe and integrate– so, when one of these anti-cancer-HIVs infects a cell, it will permanently integrate the genes necessary to fight the cancer, NOT ‘HIV-1′. You physically cannot get ‘AIDS’ from this kind of therapy.
But the cells that kill infected cells are CD8+ T-cells.
HIV-1 likes to infect CD4+ T-cells.
To get around this, they put on the outside of the anti-cancer-HIV molecules VSV-G. Know how viruses have ‘keys’ that only fit in certain ‘locks’ on the surface of your cells? Some cells cannot be infected with certain viruses because they do not have the right ‘lock’ for the viruses ‘key’? VSV-G is a skeleton key. Gets into everything.
SO! Here is what the scientists did–
- They took blood cells out of the cancer patient.
- They purified the T-cells from the blood cells.
- They infected those blood cells with an HIV-1 virus with VSV-G on its surface, that contained the genetic information for making an anti-cancer antibody/TCR.
- They then put the T-cells back into the cancer patient.
- The T-cells with the chimeric receptor killed the cancer.
- All of it.
- It also killed all of his non-cancerous B-cells (dude has no antibodies) but he is not having any recurrent infections or anything weird. Hes gardening and hanging out and doing just fine. No cancer. Not dead.
If Ive said it once, Ive said it a million times:
I LOVE THE FUTURE!!!!!!