fighting big-c. Indian-origin team gives immune cells a new sting to fight

A team of Indian-born scientists in the US has found a way to deal with cancer cells that trick the immune system to evade destruction, paving the way for a novel therapeutic method that would strengthen immune cells’ ability to seek and destroy even aggressive cancer types.

The feat achieved by the researchers led by Ashish Kulkarni of Department of Chemical Engineering at University of Massachusetts and Shiladitya Sengupta of Harvard Medical School may give immune cells a new sting in their battle against cancer cells.

The findings of the study, reported in the journal Nature Biomedical Engineering on Monday, carried out by scientists of Indian origin, including one who works with a New Delhi-based cancer research firm, Invictus Oncology.

Macrophages – immune cells that engulf and digest particles and pathogens – also help destroy cancer cells. But in many cancers, macrophages play a paradoxical role, with one class of macrophages – called M1 — rousing the immune system to action, while another subtype — M2 macrophages — quelling inflammation.

Researchers have found that cancer cells mange to escape destruction by macrophages in two ways – by converting M1 immune cells to become tame M2 macrophages and also by sending out an “eat me not” signal that tricks M1 macrophages into letting them be.

Kulkarni and Sengupta and their compatriots at Brigham and Women’s Hospital (BWH) of Harvard Medical School have developed a therapeutic that delivers a double whammy to knock out both mechanisms.

“Clinicians are increasingly realising that one drug or a one-size-fits-all approach is not enough when combatting cancer, and that a combination immunotherapy, such as blocking two distinct targets in the same immune cell, is the future of immuno-oncology. Our approach capitalises on this concept,” said Kulkarni.

Kulkarni, who hails from a small town in Maharashtra and has studied at the Institute of Chemical Technology in Mumbai, and colleagues in 2014-15 designed supramolecules – therapeutics that are built from component molecules that click together like building blocks. To reinvigorate macrophages, the team designed a supramolecule that could block the “don’t eat me” signal that cancer cells can produce and simultaneously inhibit signalling that converts macrophages to M2 subtype.

Supramolecular therapy

The researchers tested the supramolecular therapeutic in animal models of aggressive forms of breast cancer and skin cancer, comparing their drug directly with a drug currently available in the clinic. Mice that were untreated formed large tumuors by Day 10. Mice treated with currently available therapies showed decreased tumor growth. But mice treated with the new supramolecular therapy had complete inhibition of tumor growth. The team also reported an increase in survival and a significant reduction in metastatic nodes.

“We can actually see macrophages eating cancer cells,” said Sengupta, who co-founded Invictus Oncology, along with Raghunath Mashelkar, former Director general of the Council of Scientific and Industrial Research. The researchers plan to continue testing the new therapy in preclinical models to evaluate safety, efficacy and dosage. The supramolecular therapy they have designed has been licensed and they hope to move the therapeutic into clinical trials in the years ahead should preclinical testing continue to show promise.

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