For cancer immunotherapy, gently recovering lab-grown cells is key. Indian researchers may have just found a way
Kartavya Desk Staff
Immunotherapy is reshaping cancer care by harnessing the body’s own immune system to fight tumours. Among its most promising forms is CAR T-cell therapy, in which T-cells collected from a patient are engineered in labs to recognise and destroy cancer cells. But for this therapy to succeed, scientists must grow large numbers of healthy T-cells outside the body — and retrieve them. A new study from Indian Institute of Technology-Bombay, published in Biomaterials Science and featured in the European Society for Biomaterials conference collection, addresses this crucial bottleneck: retrieving these lab-grown cells without damaging them. Led by Professor Prakriti Tayalia, the team has demonstrated a gentler recovery method that preserves the cell’s viability and immune behaviour, potentially improving the reliability of advanced cancer care. This is how the method works, and why it could potentially bring down the high costs associated with immunotherapy. First, what are T-cells? T-cells are a type of white blood cells that act as the body’s frontline soldiers. They patrol the bloodstream and tissues, looking for infections or abnormal cells such as cancer. When they detect a threat, T-cells either kill the harmful cells directly or signal other immune cells to join the fight. Their ability to recognise and respond to disease makes them central to immunotherapy. What is CAR T-cell therapy? CAR T-cell therapy is a cutting-edge treatment that reprogrammes T-cells to better target cancer cells. Doctors collect T-cells from a patient’s blood and, in the lab, add a new gene that equips them with special receptors called chimeric antigen receptors (CARs). These receptors act like GPS trackers, guiding the T-cells to cancer cells. Once engineered, the cells are grown in large numbers and infused back into the patient. Globally, CAR T-cell therapy has been approved in the US and Europe for certain blood cancers such as leukemia and lymphoma. It has shown dramatic success in patients who had exhausted conventional treatments. However, it remains expensive, often costing upwards of Rs 3-4 crore abroad, and is still being tested for solid tumours. Why is recovering immune cells so difficult? This is the issue the IIT Bombay study addresses. Growing T-cells in a lab is only half the battle. They must be collected intact and functional for therapy to work. Traditionally, labs grow cells on flat plastic dishes, but this environment does not mimic the body. To better replicate natural conditions, researchers use three-dimensional fibrous scaffolds. This biomaterial resembles a dense fishing net, allowing T-cells to grow more actively and multiply faster. But this advantage comes with a challenge: cells burrow deep into the fibres and grip them tightly, making them hard to remove. “Cell recovery sounds simple on paper, but in practice it turns out to be one of the biggest challenges,” said Professor Tayalia. “Without enough healthy cells, you cannot test them properly or use them for therapy.” Dr. Jaydeep Das, first author of the study, said: “Theoretically, T-cells are considered easy to handle because they are ‘suspension cells’. In reality, when placed inside a dense fibrous network, they grip tightly.” The difficulty is even greater when scaffolds were coated with stimulatory molecules such as anti-CD3 antibodies, which are often used to activate T-cells. In these cases, cells adhered more strongly, making recovery harder. What methods did the researchers use? The IIT Bombay team tested three approaches to retrieve T-cells: manually flushing the scaffolds with a growth medium, using TrypLE (a relatively harsh enzyme), and using Accutase. Accutase is a gentler enzyme solution that was developed in the 1990s. The team measured three outcomes: How many cells were recovered, how many survived, and whether the cells retained their immune function. The study found that cell yield was comparable across all methods. The real difference, however, lay in viability and function. Cells treated with TrypLE showed higher death rates and lost important immune functionality. In contrast, Accutase-treated cells survived better and continued to function normally. They formed clusters, an essential step before division, and grew robustly after recovery. Professor Tayalia said: “Harsh treatments to cells, using enzymes such as trypsin, can damage key surface proteins needed for immune signaling and activation, reducing the cell’s therapeutic usefulness. Accutase appears mild enough to avoid this problem.” What does this mean for cancer therapies? The findings suggest that Accutase-based recovery could improve the reliability of preparing T-cells for therapy. While the IIT Bombay highlight focused on CAR T-cell treatment, the journal article situates the work within the broader field of adoptive T-cell transfer (ACT) therapies, which include CAR T-cells but also other engineered immune approaches. Professor Tayalia said about the importance of the process: “If we want these advanced therapies to reach patients, every step matters. How we grow cells, and how we retrieve them, can make a real difference.” The team also found that T-cells grown on scaffolds were more effective at killing cancer cells compared to those grown on flat dishes, pointing to a dual benefit of scaffold growth and gentle recovery. What comes next in this research? The researchers plan to test their findings in animal models and explore whether T-cell-loaded scaffolds could be implanted directly into the body. If successful, this could open new avenues for cancer treatment, where immune cells are not only prepared outside the body but also delivered in innovative ways. Why is this significant for India? India has begun its own CAR T-cell journey. IIT Bombay and Tata Memorial Centre have collaborated on early trials, with spin-offs like ImmunoACT working to make therapies more affordable. While CAR T-cell therapy abroad can cost several crores, Indian efforts aim to bring costs down to a fraction, making them accessible to more patients. For patients, this could mean therapies that are not only effective but also within reach. IIT Bombay’s work shows how small technical refinements can have potential clinical impacts.