Two small human studies using personalized cancer vaccines engineered with mutant proteins that collectively create a unique thumb print which can be used to identify and target cancer cells for a precision attack by the immune system have demonstrated strong potential in a select number of cases. And their early successes — outlined in Nature today — are outlining a path forward that many academic and industry researchers believe represents one of the next big steps forward for combinations using the leading PD-(L)1 therapies now on the market.
These first early forays in single arm studies involve technologies now in development at Neon Therapeutics and BioNTech, two biotechs on opposite sides of the Atlantic which share some common goals. And they both focused on high-risk patients who had undergone surgery to have their tumors removed.
The work done by Ugur Sahin, the CEO and co-founder of Germany’s BioNTech, involved 13 melanoma patients treated with a messenger RNA therapy containing up to ten mutated proteins identified through genetic sequencing. Of eight patients in remission at the time of therapy, all eight remained in remission after a year. Of the five who had seen their cancer spread ahead of therapy with a personalized cancer vaccine, two saw their tumors shrink. One later saw the cancer resurge while a third went into remission after the use of a PD-1 checkpoint.
BioNTech is already closely partnered with Genentech in a $310 million deal that lays the foundation for combination studies using the pharma giant’s PD-L1 drug Tecentriq. Neon, meanwhile, is pushing ahead with combinations using Bristol-Myers Squibb’s Opdivo.
The other study from Neon Therapeutics involved a smaller group of six melanoma patients treated with a personalized neoantigen vaccine, where the neoantigens selected could bind well with MHC proteins and stood a good chance of kicking up an immune response that would target the cancer cells and leave healthy tissue alone. This approach also has demonstrated potential in recruiting CD4 and CD8 T cells that can fight the cancer while also creating durability, so the vaccines can continue to do their work and hold cancer at bay.
After two years, four were without recurrence of the cancer and the two others experienced a complete response after a PD-1 was added.
“Although the numbers of people who were treated in these studies were small, both studies indicated potential benefits,” observed Leiden University’s Cornelis Melief in an accompanying editorial. One noted benefit was a reduction in metastasis.
“This research shows that it is feasible to produce peptide-based personalized neoantigen vaccines, and these vaccines can generate immune responses with reliability and potency,” said Catherine Wu, a Dana-Farber investigator and Neon co-founder. “In this study, over 70% of all peptides successfully generated measurable CD4 and/or CD8 T cell responses. In addition, while patient numbers are limited, the initial clinical data is intriguing and worthy of exploration beyond the adjuvant setting into patients with active disease with immuno-oncology combinations.”
Some big hurdles remain. The results have to be replicates in much larger studies involving many more patients. Researchers will have to identify which cancers are most likely to respond to this kind of therapy. And a manufacturing process that currently takes months will need to be cut down to a matter of weeks, notes the article in Nature. In addition, the checkpoints alone cost $150,000 a year, and a complicated personalized cancer vaccine won’t be cheap.
BioNTech and Neon are also working in a field with a number of rivals, including Gritstone and Moderna, which will likely see these new studies as further validation for their own work.
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