Dr. Ugur Sahin is trying out the same mRNA technology that underlies the Covid-19 vaccine that BioNTech brought to much of the world — along with its partner Pfizer — to try to improve the newest and riskiest approach to treating cancer: CAR-T therapy.
Sahin hopes to use a type of mRNA vaccine to improve the treatment, making it both safer and more effective — and perhaps making it cheaper in the long run. He’s presenting some very early results from clinical trials at the Society for Immunotherapy of Cancer meeting in Washington, DC.
“We are cancer doctors,” Sahin told CNN in an interview ahead of the meeting. “We are really passionate about that. What we want to accomplish is to provide really better treatments.”
CAR-T, short for chimeric antigen receptor T-cell therapy, involves taking immune cells called T-cells from each patient, genetically altering them to target the cancer, and then reinfusing them back into the patient.
Only a handful of CAR-T therapies are approved by the US Food and Drug Administration, and they cost around $400,000.
They work best against blood-based cancers, Sahin noted. He is trying the approach against solid tumors.
The trouble is toxicity. Side effects can be deadly and include a severe type of inflammation called cytokine release syndrome, and brain swelling. And trying to use the approach against solid tumors adds to this danger.
“There are only very, very few targets which are cancer specific,” Sahin said. “That makes it a bit difficult to develop a treatment which is not only effective, but safe. As safety is a big, big challenge — to have targets that don’t come with toxicity.”
BioNTech is looking at a particular molecule active on cancer cells called claudin 6. “It is not expressed in healthy cells,” Sahin said. “But it is activated and expressed in several types of cancers like testicular cancer, ovarian cancer, endometrial cancer, and the percentage of other tumors, a smaller percentage of stomach cancer, lung cancer and of some sorts of sarcomas,” he added.
“It’s an excellent target — it’s like black and white. It has no expression in normal tissue, but strong expression in these tumors. And we have created a powerful antibody, which is used as the receptor now for this CAR-T cell treatment.”
The data Sahin is presenting involves just nine patients with testicular, ovarian and endometrial cancer, plus one with a type of soft tissue sarcoma.
“This appears to be safe. We don’t see toxicity. But we see a clinical activity. We see, even at the low dose, we are starting to see shrinkage of tumors.”
The second goal is to see the T-cells multiply and thrive, in the hope they will continue to fight the cancer over time. Sahin said there’s evidence that’s happening in at least some of the patients.
That’s where the mRNA vaccine might come in. Sahin hopes to use it to help instruct the T-cells to multiply and scour the body for tumor cells — just as vaccines work over time to continue to protect people from infectious diseases. BioNTech has demonstrated it can do this in mice.
“The impact of this treatment could be two ways. On the one side, of course, a novel target for treatment of high medical need tumors. For example, ovarian cancer — advanced ovarian cancer — can’t be cured. That is really, really a huge medical challenge. Testicular cancer is the most important cancer in young males,” he said.
He believes the approaches BioNTech used to make the mRNA vaccine fast and cost-effective enough to roll out quickly for Covid-19 can be applied to hard-to-treat cancers.
“We are living in a time where we have an extremely fast innovation cycle,” Sahin said.
He’s aware CAR-T therapies are expensive and difficult to deliver. He says he does not want to become a developer of top-tier, bespoke products for the wealthy.
“We are cancer doctors. We don’t want to develop treatments for the top, top, rich people,” Sahin said. “It is it is about asking the question what can you innovate, do, to solve the problem and make it affordable?”
He declines to estimate how he could make a $400,000 treatment affordable for the world.
Instead, he speaks of “optimizing the process.” At first, he notes, messenger RNA was hard to produce and extremely expensive. BioNTech figured out how to make it cheaply and abundantly for use in a vaccine that’s now being produced by the billions.
“If there is no next, best product, then you have a product,” he said.