When the Nobel Prize for Medicine and Physiology was announced recently, it brought a smile to the face of Nitin Karandikar, MD, PhD, professor and chair of pathology.
The prize honored James Allison and Tasuku Honjo for discovering the molecules and mechanisms that put the brake on T-cell activation—discoveries that have led to new cancer treatments that unleash a patient’s immune system to seek out and destroy tumor cells.
Research on the CTLA-4 molecule that was the focus of Allison’s work is near and dear to Karandikar’s heart because it was the starting point of his own research career as a graduate student in Stephen Miller’s laboratory at Northwestern University in the 1990s.
“At the time, Jeff Bluestone’s and Jim Allison’s groups were focused on finding the function of CTLA-4, almost simultaneously showing that blocking CTLA-4 revved up the immune system in various situations,” Karandikar says.
Allison showed that inhibiting CTLA-4 had a powerful anti-cancer effect. Karandikar worked with Bluestone, who was at University of Chicago, to study this mechanism in the context of multiple sclerosis (MS), an autoimmune disease.
“When the cancer immunotherapy drugs came roaring in many years later, it was beautiful to see the molecule I had studied and showed the role of on the front page of the Wall Street Journal,” Karandikar says. "And then when I saw the Nobel Prize announcement, I just chuckled to see that this actually won the prize like I had predicted in recent years!”
Karandikar is still focused on the immune processes involved in MS, but he no longer studies CTLA-4. His group was the first to show that contrary to current thinking, CD8+ T cells that are targeted against nervous system antigens are actually protective and not destructive in MS.