Still, the promise of training the body to defend itself from cancer, and to not have to bombard patients with chemotherapy or radiation that kills both cancer cells and healthy cells, was such an elegant idea that it sparked the imaginations of scientists for decades.
Researchers identified many kinds of white blood cells and the chemical networks involved in keeping us disease free. The main actors include B cells, T cells, and Dendritic Cells (DC). The DC and the B cells are scouts, first to recognize and shine a light on the invaders. DC’s vacuum up the invaders and signal the T cells to respond. T cells, as captains of the immune system, direct and activate the responses of other T cells and B cells. B cells, armed with antibodies that lock onto the surface, neutralize the invaders. Once researchers had a better understanding of how the various players of the immune system responded, the goal became making the T cell a more effective captain in identifying and attacking cancer.
Researchers figured out how to harvest the T cells from the patient’s blood by separating them out in a specifically designed centrifuge, the one Emily had been hooked up to. Then they developed techniques for how to grow T cells in a lab by the billions, how to characterize these cells, and how to prepare them for reinfusion, thereby vastly increasing their presence in the bloodstream.
Once they had T cells, and lots of them, the next huge advancement was when they genetically engineered a synthetic molecule that could be attached to the T cells, giving them the ability to recognize and destroy cancer cells. These synthetic immune cells are called CAR T cells, with “CAR” standing for Chimeric Antigen Receptors. The CAR on the outside of a T cell is composed of an antibody that, like the naturally occurring B cell antibody, binds to the cancer antigen. The big difference from a naturally occurring antibody is that a CAR has a portion that is embedded in the cell membrane through to the inside of the cell (the cytoplasm), signaling the T cell to attack the cancer. Amazing! The problem in the early versions of CAR T cells is that they got exhausted rapidly. Not enough of them stuck around long enough to make the cancer disappear. As effective as CAR T cells were in the lab and in mice, still more work needed to be done to make the human immune system capable of knocking out cancer.
This is where June and Levine’s experience with HIV advanced cancer therapy. Dr. June had studied how the HIV uses the T cell as a host. It breaks through the T cell membrane and takes over, slipping its genes into the T cell chromosomes, so the T cell produces the virus that in turn destroys it and other T cells. Dr. June figured out how to combine cutting edge technologies and apply these to help cancer patients. First, he knew that researchers had shown that it was possible to take out the genes that made HIV a killer and use its powerful delivery mechanism to place the gene for the cancer-killing CAR inside that modified T cell. The disabled HIV delivers the gene that scientists designed, but it could never cause HIV disease in the patient. Dr. Levine brought all his experience in engineering T cells to growing them in a clean room laboratory with microscopic beads that produced billions of CAR T cells. When these specially modified cells were infused into a patient with cancer, the cancer-killing CAR T cell continued to replicate inside the body, thereby creating a living cancer killing drug that could stay on the job until the cancer was completely gone.
Dr. June compares the disabled HIV delivering the CAR gene to the Trojan horse from Greek history. The Greeks were losing a ten-year war against the Trojans when they came up with the idea for a sneak attack. The Greeks pretended to surrender and left a tribute for the Trojans in the form of a huge wooden horse, with a note announcing their withdrawal and defeat. The Trojans wheeled the big horse inside the walls of the city and started celebrating when suddenly a trap door opened in the horse’s belly and out popped the Greek special forces, who won the battle. This would be Dr. June’s brilliant sneak-attack to put the gene for the CAR hidden in the belly of the disabled HIV that would create the CAR T cell that would slay the cancer.
As Dr. June described it to me later, “When the CAR T cells are injected, they act like supercharged killers on steroids. The Trojan horse of the HIV slips through the cells’ defenses and heads straight to the tumor, where those chimeric cells divide, quickly numbering hundreds of millions of cells specifically programmed to destroy the cancer.”
What a fantastic idea, this hybrid serial killer of cancer. Just one CAR T cell can kill 1,000 tumor cells. Yes, that’s right: a ratio of 1-to-1,000. There is no precedent for this in cancer medicine. With every other medicine, you ingest it, metabolize it, and then take another dose. CAR–T cell therapy is the first living drug, capable of regenerating in the body for years.
During that six-week wait for the T cells to be reprogrammed, we had to be careful not to expose Emily to germs because if she got an infection it might delay her participation in the clinical trial. We washed our hands carefully every time we entered her room and wiped down any item that came in, lest it carry germs to Emily. As the day of the infusion approached, we were relieved we’d succeeded in keeping her safe.
The week before getting her CAR–T cell infusion, the hospital was buzzing about Emily. If this worked, Emily and
