Hot topic: Is the wind about to change for cell and gene therapies?

Cell and gene therapies have had a tough few years. Investors, their heads turned by weight loss drugs and put off from taking longer-term bets by higher interest rates, appear to have hardly noticed them.  

The sector is certainly facing challenges – not only sentiment, but practical hurdles too. But is the wind about to change?  

These were some of the issues discussed in a recent webinar, The State of Cell and Gene Therapy, hosted by the publication Genetic Engineering and Biotechnology News (GEN). 

Key takeouts?  

• There are challenges aplenty – manufacturing bottlenecks and the extremely high price of the resultant medicines being among them; 

• Sentiment’s certainly been better – although that’s something that can change relatively quickly;  

• There’s a huge amount of scientific advancement going on right now, that’s sooner or later going to break the surface in terms of exciting clinical trial results. 

Michel Sadelain, winner of the 2024 Breakthrough Prize in Life Sciences for his pioneering work developing CAR-T therapy, was upbeat. 

He said recent advances in the chimeric antigen receptor (CAR) field “remind me of the Cambrian explosion [in life forms] that happened 500 million years ago”. 

It’s now eight years since the FDA approved the first CAR-T therapy, Kymriah, which is used to treat certain leukaemias and lymphomas. Since then, the FDA has approved another six CAR-Ts, all to treat blood-based cancers. 

With CAR-T therapies, blood is first taken from the patient and their T cells from that sample isolated. Then these T cells are genetically modified to express CAR receptors capable of recognising a particular cancer cell antigen, such as CD-19. The manipulated cells are then multiplied hugely in number (a process called expansion), before they are all put back into the patient.  

But CAR-Ts have proved largely ineffective in treating solid tumour cancers. However, that didn’t mean they would never work in them, said Sadelain. It was merely the case that “solid tumours are beyond the capabilities of the first generation of CAR-Ts, that were designed for bloodborne cancers.” 

Many scientists are currently working “to overcome the molecular, chemical and physical barriers” for CAR-Ts to work in solid tumours, Sadelain added. 

Dr John Maher, CSO of London-based Leucid Bio, who undertook pioneering work engineering and testing second generation CAR-T technology in human T cells while a fellow in Sadelain’s lab, told Optimum:  “We are now seeing meaningful progress towards producing effective CAR-T solutions for solid cancers, with particularly impressive recent data in neuroblastoma and CNS tumours. 

“For instance, we at Leucid are very excited about our LEU011 adaptor CAR, which is about to be evaluated in the AERIAL clinical trial, treating patients with common adult-onset solid tumours. So we too firmly believe that CAR-T therapies hold huge potential for treating solid tumours.” 

The webinar also heard that there’s also a huge amount of progress being made in a host of other types of cell and gene therapy – for example, with gene treatments for rare types of blindness and hearing loss now in clinical trials. 

Dr Federico Mingozzi, former CTO and CSO at Spark Therapeutics, who has been instrumental in developing adeno-associated viruses (AAVs) as vectors to ‘smuggle’ genetic therapies into cells, was optimistic about the prospects. 

“I feel there is still so much interest and so much great work, and so many great technologies that are starting to give good results,” he said. 

“If we keep going, we will see a lot of fantastic results,” he enthused. “So, it’s not the moment to give up. It’s the moment to push through at full speed, because [the work] is going to have a great impact on quality of life for patients – which is the thing, at the end of the day, that we care most about.” 

So much for the optimism. What of the challenges? 

Manufacturing, particularly of cell-based therapies, remains “a bottleneck” admitted Sadelain. But he said there were “many shots on goal” to improve the situation, be that by scaling up cell production (something being tackled by French firm Astraveus), or by making “fewer, better cells.” 

Once manufacturing has been scaled up, costs should come down – so addressing another key criticism of cell and gene therapies, that they are too expensive for mass use.  

Other researchers are working on new exciting possibilities such as in vivo gene editing, which would speed up the treatment process itself, and the development of ‘off-the-shelf’ allogeneic cells. Both developments could significantly reduce costs. 

Another hurdle is regulation – specifically, the need to go through a whole new approval process, including lengthy safety protocols, for gene treatments that are based on exactly the same technological platform. 

Mingozzi said constructive discussions were taking place with the FDA to “streamline” regulation processes where there were “standardised manufacturing” processes. If these discussions yielded results, he said, that could lead to quicker development times – which should eventually feed through to lower cost medicines. 

He explained: “If you keep everything the same and what you change is maybe just the gene of interest, then you could actually contribute to further decrease the cost of drug development. 

“I have seen open minded attitudes [about streamlining regulation] from the FDA … and we will see. That’s something to look for in the coming months and years.”