PACT Pharma says it's perfected the tech to select neoantigens for personalized therapy — now onto the clinic
At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.
It’s a key step in making immuno-oncology work for everyone because scientists can now pinpoint what exactly is driving, say, patient response to checkpoint inhibitors, according to the team behind the work — opening the door to eliminating solid tumors.
Working with some immune cells captured from a patient who had a long-lasting response to anti-PD-1 therapy, researchers ran the sample through their “ultra-sensitive and high-throughput” isolation technology, dubbed imPACT. After retrieving the T cells that they believe were responsible for the response, they engineered (with non-viral gene editing) other T cells to express those same receptors and demonstrated the resulting T cells can kill the same person’s cancer cells.
With backing from the Parker Institute for Cancer Immunotherapy, Cristina Puig-Saus led the study at UCLA, where PACT co-founder Antoni Ribas directs the tumor immunology program at the Jonsson Comprehensive Cancer Center. Ribas is listed as a senior author.
“We hope that a better understanding of the T cell responses that occur after immune checkpoint blockade will guide the design of personalized adoptive T cell therapies,” Puig-Saus said in a release accompanying their presentation at an AACR special conference days ago.
Once PACT gets to clinical studies — and it’s recruiting for a Phase I now — it would also have to show it can quickly expand the population of those T cells and safely reinfuse them into the patients.
“While it is early, the results demonstrate the possibility for PACT’s approach to ignite a patient’s immune response directly against their unique tumor mutation signature, within a clinically relevant timeframe, with potential applicability to most cancers and all ethnicities across the globe,” CEO Alex Franzusoff said in a statement.
The approach puts a twist on CAR-T and next-gen TCR therapies, which recognize a fixed set of antigens shared among patients. Cancer vaccines are often too slow to catch up with tumor growth; tumor-infiltrating lymphocytes are hard to manufacture in vast quantities, the company wrote — problems that other startups such as Neon Therapeutics and Iovance are attempting to address.
PACT, of course, will also face its own challenges in advancing a tailor-made immunotherapy. From a paper quoted on its website:
Personalizing the immune effectors used and the cancer antigens targeted will require reconciling timescales of clinical need, on-demand manufacturing, and regulatory compliance.
With a star-studded founder team — including Ribas, David Baltimore, Jim Heath, Terry Rosen and Juan Jaen — and a well-heeled syndicate that’s poured in $126 million, PACT is ready to tackle the challenges head on.