When the immune system detects a protein from a pathogen,
it’s supposed to dispatch killer T cells to eliminate the invader.
Some cancers can interfere with this process by hijacking the checkpoint proteins that keep our immune system from revving out of control
and using them to turn T cells off.
Starting in the mid-1990s, several research teams found success by treating mice with #checkpoint #inhibitors,
-- then a new class of drugs designed to keep tumor cells from concealing their identity and signaling, effectively, “nothing to see here.”
Thirty years on, checkpoint inhibitors have become a transformative tool in cancer treatment, especially for melanoma.
The research that went into developing checkpoint inhibitors showed conclusively that immune cells detect cancer much in the same way they identify other pathogens:
through differences in protein structure determined by DNA
—a crucial insight.
But as revolutionary as checkpoint inhibitors have been for immunotherapy, they don’t work for everyone
—far from it.
Some 80 percent of patients do not respond to this class of drugs.
Researchers are still trying to understand all the mechanisms that play a role in determining who does respond,
but one key factor is whether the immune system is able to recognize tumor cells on the basis of their mutations.
This is where mRNA vaccines come in.
#Jason #Luke, a melanoma researcher who now serves as chief medical officer of mRNA-medicine start-up #Strand #Therapeutics,
helped to design several ongoing clinical trials of mRNA vaccines for cancer.
He explains that both checkpoint inhibitors and mRNA vaccines build on our deep evolutionary adaptation for fighting pathogens
by identifying the proteins they shed in our bodies.
But checkpoint inhibitors are effective only if the patient’s immune system recognizes the cancer as a threat.
In contrast, mRNA vaccines have the potential to work even in patients whose cancers haven’t spurred much immune response.
The trick, Luke says, is using computational tools to decipher which of a given tumor’s mutations are most likely to be found by the immune system.
#MichaelMemoli
#WilliamColey #immunotherapy #stroma #MHC
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