Personalized…Off-the-shelf.
Well-tolerated…Potent.
Accessible…Cell therapy.
Contradictions? Or ingredients for the next blockbuster cancer treatment?
That’s the proposition behind emerging therapeutic company BriaCell: combine the advantages of cell therapy without inheriting its traditional limitations.
According to BriaCell President and CEO Dr. William Williams, “With good clinical data, I think it has the potential to change the way cancer is treated.”
Good clinical data is key, and BriaCell hopes to release just that from a late phase III breast cancer trial wrapping up this fall. Nature Medicine highlighted their study of candidate Bria-IMT as one of 11 clinical trials to watch this year.
A few things make this trial exciting:
- It’s inclusive: All breast cancer subtypes, extensive prior treatment, progression to brain metastases
- It’s promising: Earlier trial data shows a strong immune response and metastatic tumor regression with a relatively mild safety profile (primarily injection site irritation)
- It’s transformative: The key innovations behind Bria-IMT can be expanded to a variety of cancers. An analogous therapy for prostate cancer is already in the clinic under open IND, with lung and melanoma next in line and ovarian further down the pipeline.
- It’s easy to administer: Off-the-shelf, cryopreserved cells delivered by intradermal injection (not infusion)
Describing his vision for where the platform could go, Dr. WIlliams says: “Simple intradermal inoculations that can be done in a physician’s office with these, irradiated cells that arrive after overnight shipping, kind of like an Amazon delivery.” He adds that administration could potentially even happen at home with a visiting nurse.
Notice: I did not say Bria-IMT is personalized. Let’s step back for a moment.
Bria-IMT is an engineered human breast cancer cell line that expresses breast cancer antigens (which are recognized by the immune system) and GM-CSF, an important immune-stimulating protein. There’s much more about Bria-IMT that’s interesting, but I’ll come back to that in a moment.
BriaCell’s platform Bria-OTS builds on the innovations of Bria-IMT but introduces another critical component: HLA type matching. HLAs are cell surface proteins that help the immune system recognize “self” from “invader.”
The Bria-IMT trials have suggested that patients with an HLA type similar to the engineered cell line respond better to treatment. So, BriaCell has engineered a line of cancer cells with 15 unique HLA types, which together match 99% of patients.
So, the BriaCell platform promises cell therapies that are personalized—HLA-type matched, but also ready to ship out to even rural clinics and patient homes. Dr. Williams puts it simply: “Personalized to maximize efficacy, and yet off the shelf, which makes it really easy.”
HLA-type matching was not a function of the initial Bria-IMT trials, but HLA proteins became a fascinating part of the story anyways. While Type-I HLA proteins are expressed in all cells, there is another type of HLA protein called HLA-II that is typically only expressed in immune cells. Bria-IMT cells express both.
And according to Williams, those HLA class II molecules aren’t simply present: “Our HLA class II molecules are functional,” he said, and “[Brioa-IMT cells] are capable of stimulating both helper and killer T cells.” The former is specific to HLA-II, so this mechanism may help explain their potency.
If that wasn’t enough, Bria-IMT is also combined with a unique regimen of low dose cyclophosphamide (to reduce immune cell regulation), interpheron-alpha (to boost immune response), and a checkpoint inhibitor (to eliminate the tumor cells’ defense).
Williams describes the logic as putting the immune system’s accelerator and brakes in opposite directions: “now we have the ability to neutralize the PD-L1 effect, so basically that takes the foot off the brakes of the immune system, while we’re putting the foot on the gas.”
In other words, in the immune arms race, it pulls out all the stops.
But the bigger question is whether all of those pieces can translate into something that actually helps patients, and which ones stand to benefit most.
Early trials validated Bria-IMT’s potential to generate meaningful antitumor immune responses, with tumor regression, prolonged survival, and a relatively mild safety profile in heavily pretreated patients.
But early trials can only tell us so much.
The Phase III trial is designed to answer a much harder question: Can Bria-IMT actually help patients live longer than the treatments they would otherwise receive? Rather than comparing outcomes with historical data, the randomized trial pits Bria-IMT against physician’s choice, with overall survival as its primary endpoint.
“In our Phase 2 study, we beat the historical data. We basically doubled overall survival, or close to doubled it.,” said Dr. Williams, and in Phase 3: “We’re going full bore with overall survival as our endpoint.”
If those results are positive, they could provide clinical proof for a different model of cell therapy: one that is manufactured in advance, shipped off the shelf, administered with a simple injection, and potentially personalized through HLA matching.
