Chapter 90
Cancer — 17
Each bay houses its own “single use personalized RNA+” machine, a refrigerator-sized unit that cranks out long strands of mRNA encoding up to thirty-four specific cancer mutations. The mutations correspond to different neoantigens, neatly arranged in a sequence. A mixing device then encapsulates the mRNA in fatty nanoparticles to enhance its stability and cellular uptake.
And of course, AI helps identify the ones that suit the particular individual.
Apersonalized vaccine known as mRNA-4157, coming in an mRNA nanoparticle package just like the COVID vaccines, has in a randomized trial proven more effective in combination with pembrolizumab than pembrolizumab alone in battling melanoma. A three-year follow-up of an mRNA nanoparticle vaccine for pancreatic cancer that was personalized using antigens found in a resected tumor showed a persistently elevated immune response and delayed recurrence. A similar approach has been used in patients with non–small cell lung cancer, directed toward stimulating dendritic cells, a type of immune cell. Rejuvenating the aged immune system’s dendritic cells to eradicate tumors in old mice begs for testing such an approach in people with cancer. The extensive number of RNA-based vaccines in ongoing clinical trials for nearly all solid tumor types is notable.
Such results are telling us that there is plenty of room for improvement by maxing out the immune response to cancer via combinations of approaches. One that is attracting considerable attention is engineering T cells known as CAR-T for chimeric antigen receptor (CAR)-T cells. It’s cell therapy for cancer that already has multiple FDA approvals for different blood cancers, with more than forty thousand patients treated in the United States alone. Solid tumors, which account for the vast majority, are not yet responding as well to this approach, but progress is being made.
CAR-T therapy involves removing the T cells from a patient with cancer, sequencing the cell’s DNA and RNA, and using that information to specifically activate the T cells against the person’s cancer, then reinfusing the cells back to the patient. This, along with the use of personalized neoantigen vaccines, can be considered the quintessential individualized medical intervention. In the first patients receiving CAR-T cells delivered to the brain for recurrent glioblastoma, one of the most fatal cancers known, there was rapid and dramatic regression of tumors. That type of excellent brain tumor response was also seen with an intravenous administration of an mRNA with lipid particle aggregates. It is remarkable to see how engineered T cells and cancer vaccines have evolved together. They have broadened the ways we can improve a person’s immune response to cancer. The number of combinations of different ways to fire up the immune system to fight against cancer is astounding, now including CAR-T, oncolytic viruses, antitumor antibodies, vaccines, BiTEs, activating dendritic cells, gut microbiome modification, and small molecules. It is hard to grasp just how much better we are becoming at deploying the most bespoke treatment for a given individual.