Hope for stomach, brain cancer? Cancer-fighting immune therapy works on solid tumours in early trials
Despite a failed bone marrow transplant, Delhi's Dr (Col) VK Gupta beat his blood cancer after receiving CAR T-cell therapy at Tata Memorial Hospital. Not only did he recover, he was able to go back to work in his outpatient clinic. He is among those with blood cancer who has benefitted from this cutting edge cancer treatment that re-engineers the body's own immune cells, enabling them to fight the cancerous ones. Can this therapy now work for solid and hard-to-treat tumours as well?
Earlier this month, there was good news on this front with two studies indicating increase in life span. Positive results from the first ever phase II trial of CAR T-cell therapy for solid cancers — those in the form of gastrointestinal tumours — were published from China. Another early study on the impact of a double target CAR T-cell therapy on a very difficult-to-treat brain cancer was also published in the US. 'With so many people working on the problem, it is possible that we could soon see CAR T-cell therapy for solid cancers. While the results are unlikely to be as dramatic as we have seen with blood cancers, any hope is good when survival otherwise is just a couple of months,' says Dr Hasmukh Jain, a specialist of blood cancers from Tata Memorial Hospital. He collaborated with the IIT Bombay team that developed the country's first CAR T-cell therapy.
CAR T-cell therapy essentially uses a cancer patient's own immune T-cells and engineers them in a laboratory to add receptors that can bind specifically with the cancer cells only. These engineered cells are then multiplied and infused in the patient. Usually, the cancerous cells have the ability to hide from the unmodified T-cells. However, with the new receptors on the T-cells, they cannot. The body's immune system then kills the cancer cells.
This, experts say, is because it is much more difficult to target solid cancers than blood cancers. 'One of the biggest problems with CAR T-cell therapy for solid cancers is that there aren't enough good targets. Several of the solid cancer markers are also found on normal, healthy cells, so they cannot be used. There have been cases of pulmonary toxicity with therapies whose target was expressed in small quantities in the lungs. Or, take for example, the BRCA gene mutations in breast cancers; these are expressed by other healthy cells as well,' says Dr Mayank Singh, associate professor of medical oncology at AIIMS-New Delhi.
Another challenge is that the same type of cancer may be molecularly very different in different patients — or even within the same patient — making it extremely difficult to find a suitable target for CAR T.
Besides, solid tumours are a more complex disease, says Dr Jain. 'Unlike blood cancers, other cancers are not in the blood where the T-cells are. So, they have to find the tumour and enter it. This is difficult as the T- cells are not able to effectively penetrate the tumour microenvironment or the immediate area round the tumour,' he explains. This is hostile towards immune cells and can deactivate them, including the modified T-cells given to patients.
The phase II study from China showed that the outcome was better with the new CAR T therapy as compared to the therapy generally prescribed by the physician. Patients with gastrointestinal cancers carrying a specific mutation called CLDN18.2 — having received two unsuccessful treatments previously — were given either the new therapy or existing treatments. The study found that 35 per cent of the patients given the new treatment responded as compared to 4 per cent of those on existing treatments.
Those on the new therapy also lived 2.4 months longer on average as compared to the control group.
Another new CAR T-cell therapy, which used two targets instead for a very difficult to treat brain tumour called glioblastoma, showed promise in a trial conducted at University of Pennsylvania. The tumours became smaller in nearly two-thirds of the patients with recurrent glioblastoma who received the novel therapy. And, several of the patients have already lived 12 months or longer, which is significant considering that people with this type of cancer typically survive only for six to ten months.
Importantly, the researchers also found evidence to suggest that the modified T-cells remained in the patients' immune system and continued to prevent tumour growth over time.
Experts say that studies on brain and spinal cancers called gliomas and those targeting CLDN18.2 are probably at the most advanced stages of development and may be approved within a few years. 'Now, researchers are using AI to identify suitable targets for CAR T therapies. This is the reason for the recent increase in trials,' says Dr Singh.
The IIT Bombay-incubated start-up ImmunoACT is also working on a therapy that can work on brain and nerve cell cancers called glioblastoma and neuroblastoma. Another therapy that it is pursuing will work on the gastric and gastroesophageal junction cancers — the same cancers as the Chinese trial looked at.
Anonna Dutt is a Principal Correspondent who writes primarily on health at the Indian Express. She reports on myriad topics ranging from the growing burden of non-communicable diseases such as diabetes and hypertension to the problems with pervasive infectious conditions. She reported on the government's management of the Covid-19 pandemic and closely followed the vaccination programme.
Her stories have resulted in the city government investing in high-end tests for the poor and acknowledging errors in their official reports.
Dutt also takes a keen interest in the country's space programme and has written on key missions like Chandrayaan 2 and 3, Aditya L1, and Gaganyaan.
She was among the first batch of eleven media fellows with RBM Partnership to End Malaria. She was also selected to participate in the short-term programme on early childhood reporting at Columbia University's Dart Centre. Dutt has a Bachelor's Degree from the Symbiosis Institute of Media and Communication, Pune and a PG Diploma from the Asian College of Journalism, Chennai. She started her reporting career with the Hindustan Times.
When not at work, she tries to appease the Duolingo owl with her French skills and sometimes takes to the dance floor. ... Read More
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