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How are the CAR-T cells doing?


It has been more than five years since the first CAR-T therapies, Kymriah® and Yescarta®, received market authorisation from the FDA and the EMA as next-generation cancer treatments. How are they doing now?


Despite the hefty price tags (close to half a million dollars!), their arrival still stirred up considerable global hype. That is hardly a surprise given the tremendous unmet need – reflected by the 20 million new diagnoses and 9.7 deaths cancer-attributable deaths in 2022.


Despite insufficient real-world evidence, both therapies secured reimbursement in the form of outcome-based agreements from many governments around the world, such as the UK, Spain and Germany.


Both therapies have shown impressive results, but the unfortunate news is that neither therapy can be the saviour of all cancer patients. They are, at least currently, only effective against cancers in aqueous environments, such as leukaemia – blood cancer.


CAR-T stands for chimeric antigen receptor (CAR) T-cell. These are engineered white blood cells that can specifically target and destroy cancer cells. They are powerful but a little helpless against solid tumours, for a few reasons. They have a hard time getting into the tumour, surviving the harsh environment inside the tumour, and if they survive, they need to fight hordes of cancer monsters that all look strange in their different ways. I hope they are getting paid enough for this.


But a team of scientists showed the other possibility this month. By getting the T-cell to simultaneously recognise two molecular targets that are commonly present in tumours (in this case, epidermal growth factor receptor and interleukin-13 receptor alpha 2), the levelled-up T-cell shrunk the size of solid glioblastoma tumours, a type of brain cancer that is one of the most aggressive out there. The same approach is used by another research team to produce promising results.


This new development could bring hope to wider demographics of cancer patients. Nevertheless, considering the small sample sizes of both trials, the next stage will have to be confirming that the effects are both 1) attributable to the CAR-T and 2) not just temporary. A more complex engineering process also means that these improved therapies could be even more expensive.


The other good news, this time, is delivered by a small Indian biotechnology company ImmunoACT. Their CAR-T product, NexCAR19, only costs between US$30,000 and US$40,000, which is less than 1/10 of a typical CAR-T therapy, all with improved drug tolerability. The lower cost was not entirely due to the cheaper labour in India, as the haters may say. The company has made considerable effort to optimise the production process for scaled-up production, an example of which is improving the transfection process, where a virus (lentivirus to be more specific) transforms a noob T-cell into a cancer-fighting T-cell.


The company is actually racing alongside other competitors within India, some of which have extensive collaboration with foreign researchers (we <3 international collabs). While we wait for the competition to drive down costs even further, we can also see the current and potential contribution of BRICS and other Global South countries in the global health space, each with their unique advantages, which really cannot be underestimated.


Not only will cheaper CAR-T therapies give much-needed access to cancer patients worldwide, if they are proven to be effective, I believe they will also impact each country’s healthcare “best buy” strategies in the next decade. After we celebrate the incredible advancements in cancer treatments, we need to be reminded that the leading risk factors (and strong predictors) for cancer globally are actually behavioural in nature, such as smoking, unsafe sex and alcohol abuse. As an (unapologetically) avid supporter of social interventions, I sincerely hope to see more spotlight on the social and economic determinants of cancer, such as adverse industry interests and poor access to diagnostics. We have witnessed time and time again the social interventions with cost-effectiveness that medicines just can’t compare. 


Thoughts? 


Photo credit: Science Photo Library on Canva


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