Argentine biochemist Rabinovich pursues immune system 'switches' to transform cancer treatment

Gabriel Rabinovich's path to becoming one of the world's leading immunologists began not in a prestigious laboratory, but in a hallway. The Argentine biochemist, now 57, had arrived late to secure a spot in the immunology lab where he wanted to write his thesis. Instead, he ended up in a modest space at the end of the corridor, where researchers were experimenting with chicken retinas. It was there, learning to manufacture antibodies in rabbits against retinal proteins, that he met his first mentor and discovered the scientific obsession that would define three decades of work: galectins, a family of proteins that regulate how the immune system responds to threat.

What Rabinovich found in those early experiments was elegant and troubling. Galectin-1, the protein he focused on, operated like a molecular switch with two faces. On one side, it helped the immune system return to normal after fighting an infection or disease, essentially telling lymphocytes when the danger had passed and they could stand down. On the other side, tumors had learned to exploit this same mechanism, hijacking galectin-1 to kill immune cells and slip past the body's defenses. Rabinovich called it the "sweet case of Doctor Jekyll and Mister Hyde"—a discovery in the early 2000s that opened entirely new avenues for treating both autoimmune diseases and cancer.

Three decades later, Rabinovich is still chasing that molecular switch. Last year, he joined the CaixaResearch Institute in Barcelona, a newly inaugurated research center funded by the La Caixa Foundation and dedicated to immunology. The facility, nestled at the foot of Collserola mountain, represents a shift in how scientists think about the immune system itself. Rabinovich and his colleagues are preparing experiments to modulate galectin switches in diseases like multiple sclerosis and cancer—work that could transform treatment for patients who have exhausted other options.

Immunotherapy revolutionized cancer care. It taught the immune system to recognize and attack tumors in ways that conventional chemotherapy could not. But the revolution was incomplete. Many patients saw no benefit. Others developed resistance. Tumors, it turned out, are adaptive adversaries with multiple escape routes. Rabinovich's research on galectins offers an alternative pathway for those patients, a way to block one of the mechanisms tumors use to hide. "My biggest dream," he said in an interview at the new institute, "is that we never again have to tell a patient there is nothing more we can do."

He is careful not to oversell the prospect. When asked if this dream is realistic, he called it a utopia—something he hopes to work toward without certainty of reaching it. What he does believe is that galectin-based therapies could open a door for patients who currently have none. In 2014, he predicted that cancer would become a chronic disease within twenty years. Eight years remain. He has since refined that prediction: some tumors have indeed become chronic, held in check by immune modulators that do not cure but control. Others have moved into remission, a word that was forbidden in immunooncology when he began his career. The landscape has shifted, though the battle continues.

The immune system, Rabinovich emphasizes, is far more than a defensive force. It is a system of balance, constantly sculpting the physiology of tissues, regulating digestion, kidney function, the cardiovascular system, the brain. We carry more microbial cells than human cells in our bodies, and those microbes keep the immune system alert and alive. The system patrols continuously, maintaining equilibrium. Understanding this has led immunologists to ask a new question: not how does the immune system protect us from disease, but how does it maintain health? The CaixaResearch Institute will investigate this through the lens of the exposome—the sum of all environmental exposures that shape immune function, from diet and air quality to pesticides and contaminants. What Rabinovich and his peers are learning is that the immune system remains largely a mystery, and that mystery is where the next generation of treatments will be found.