Two biotechs aim to broaden the reach of cancer immunotherapy by applying gene editing tools to an emerging form of cell therapy through a wide-ranging collaboration.
The agreement, between CRISPR Therapeutics and Nkarta, includes three components. The biotechs will first co-develop two therapies that use natural killer cells, the body's front-line defenders and Nkarta's focus, to go after tumors. CRISPR will also lend its gene editing technology to Nkarta to soup up a group of its own cell therapy products. Third, and perhaps most ambitiously, the biotechs aim to make a complex and unusual treatment that would harness both NK cells and the T cells CRISPR has been using in its own treatments.
"We have this combined vision about where the field is going in the future," said CRISPR CEO Sam Kulkarni, in an interview. "You can very well envision a world where there are NK cells and T cells in the fight against cancer together."
The deal is part of a broad, ongoing effort by the biopharmaceutical industry to expand the reach of cell therapies, which, though powerful when they work, are logistically complex and remain limited to several blood cancers.
Novartis' Kymriah and Gilead's Yescarta and Tecartus, all approved in the years since 2017, can drive certain lymphomas into remission. A similarly effective type of product from Bristol Myers Squibb, Abecma, just became available for multiple myeloma patients and another, from Johnson & Johnson, could soon follow.
But these treatments, known as CAR-T therapies, require expensive, multi-week manufacturing processes. They have struggled commercially and can sometimes trigger severe neurological and immune-related side effects. By relying on genetically altered T cells, they only use the "adaptive" component of the immune system, the body's second wave of attack.
Significant efforts are underway to move beyond those limitations. Companies like CRISPR and Allogene Therapeutics, for instance, have been trying to make more convenient, off-the-shelf T cell treatments that genetically modify cells from healthy donors rather than individual patients. More recently, a new breed of companies, like Nkarta and Fate Therapeutics, have begun advancing treatments that recruit NK cells, which, unlike T cells, are involved in the body's initial, "innate" immune response.
NK cell-based treatments are thought to be safer than their T cell counterparts and cheaper to produce. NK cells can readily distinguish tumor cells from healthy ones and have what Kulkarni described as "unique killing capability," making them a potential weapon against solid tumors.
With their first joint program, for instance, Nkarta and CRISPR are aiming at a protein target, CD70, that's commonly expressed on tumors of the pancreas, lung and more. (They aren't disclosing the target for the second co-developed program.)
NK cells are "becoming a very important tool and cell type within this fight against cancer," Kulkarni said, which drew CRISPR to Nkarta. Their progress was on display at the American Academy of Cancer Research's virtual meeting last month, where a treatment from the MD Anderson Cancer Center showed promising early results against a type of lymphoma.
But NK cells have limitations, too, such as the length of their effects versus the more durable responses seen with T cell treatments.
Genetically engineering NK cells to give them new abilities, like more tumor-killing punch or durability, is one answer, which is why Nkarta sought to gain access to CRISPR's technology. Gene editing gives NK cells "even more activity" and boosts their chances against solid tumors, said CEO Paul Hastings in an interview.
"We would not bring a CD70 program forward in a solid tumor without genome engineering," Hastings said.
The deal gives Nkarta the chance to use CRISPR's technology on five unspecified gene targets which could be modified in any of its cell therapy programs.
But it will also lays the groundwork for a project that both Kulkarni and Hastings described as in its earliest stages, to combine NK cells and T cells into a single product. Both acknowledged the difficulty of the undertaking, which would involve multiplying the genetically engineered cells separately before mixing them together.
"There'll be challenges to get there," Hastings said, "but that's what we're willing to work on together."