• Immuno-oncology has quickly become the leading field for cancer treatment innovation
  • Biotech company, BriaCell Therapeutics Corp., is an emerging leader in breast cancer therapeutics, with its innovative combination studies and its novel off-the-shelf personalized immunotherapy for advanced breast cancer
  • BriaCell’s personalized off-the-shelf cancer treatment is expected to enter the clinic within a year

Until recently, the predominant forms of cancer treatment have been: radiation, chemotherapy, targeted therapies, and surgery. In the last ten years, however, a new pillar of therapy has emerged to join the ranks of these tried and tested treatments. Immuno-oncology, also referred to as immunotherapy, has rapidly evolved into a viable treatment option for cancer patients.

In essence, immunotherapy drugs stimulate the body’s own immune system to attack cancer cells. With this leap in technology giving rise to an entirely new way of approaching cancer, many big pharma, biotech and startup companies are following the curve of innovation and reallocating their resources. This has led to immuno-oncology experiencing a double-digit growth rate, which is currently on track to reach USD 97.34 billion by the end of 2022.

Because of immuno-oncology's impressive growth within a relatively short period of time, many biotechnology companies are creating strategic partnerships with larger companies to maximize potential.

BriaCell Therapeutics Corp. (TSXV: BCT) is a biotechnology company that is developing safe and effective immunotherapies for cancer. BriaCell has recently partnered with Incyte Corporation — a company with a rich portfolio of immunotherapies for cancer, described in further detail below. Additionally, the company is currently conducting a Phase I/IIa clinical trial of Bria-IMT™, its lead candidate, in combination with pembrolizumab (KEYTRUDA®); manufactured by Merck & Co., Inc. The Combination Study is listed in clinicaltrials.gov as NCT03328026. Apart from this, BriaCell is developing the first off-the-shelf personalized immunotherapy for advanced stage breast cancer, which is expected to enter the clinic within a year.

BriaCell’s Bria-IMT™ shows incredible potential for cancer treatment

BriaCell’s immunotherapies include Bria-IMT™, a breast cancer cell line engineered to activate the immune system, and Bria-OTS™, BriaCell’s novel off-the-shelf personalized immunotherapy, which works to “awaken” the immune system that has been shut down by the cancer.

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Bria-IMT™ immunotherapy stimulates the body’s immune cells to attack and destroy tumors.

Dr. William V. Williams, President and CEO of BriaCell, says that certain treatments that aren't commonly effective in fighting cancer cells on their own can be used to great effect when paired with other immunotherapies.

"Cancer cells are extremely adaptable," Dr. Williams says. "When a treatment knocks down some cancer cells, other cancer cells can survive because they evade the initial immune response." This is the rationale behind BriaCell's ongoing combination study of Bria-IMT™ with KEYTRUDA®.

Bria-IMT™ has a unique mechanism of action that makes it able to work well with drugs such as KEYTRUDA® to create a more potent and active immune response. KEYTRUDA® essentially acts as a performance booster. Moreover, Dr. Williams notes that BriaCell has seen evidence of synergistic or additive activity of the combination in advanced breast cancer patients already.

"Bria-IMT™ is putting the foot on the gas of the immune response in a very targeted way, while KEYTRUDA® and other molecules like it work by taking their foot off the brakes of the immune response, but in a very general way,” notes Dr. Williams.

A positive pairing

The idea behind the innovative combination study used by BriaCell comes on the heels of a significant breakthrough by American and Japanese scientists. Doctors James P. Allison and Tasuku Honjo discovered a way to reprogram the body’s immune response to cancer cells through molecules that act as immune “checkpoints” including CTLA-4 and PD-1. For their discovery, both doctors received the 2018 Nobel Prize in Physiology and Medicine.

On its own, Bria-IMT™ has already achieved positive proof-of-concept in women with advanced breast cancer, but when paired with humanized antibody, KEYTRUDA®, it is expected to show further benefits.

KEYTRUDA®, while not effective against breast cancer on its own, can block PD-L1 activity, awakening a component of the immune system to give Bria-IMT™ the extra leeway it needs to activate an anti-tumor response.

While the Bria-IMT™/KEYTRUDA® combination is still in Phase I/IIa testing of its FDA approved combination study, Dr. Williams is excited about early results and the potential solution for advanced breast cancer patients who face a grave outlook and have few treatment options.

Partnership with Incyte Corporation

BriaCell has recently partnered with Incyte Corporation to see how far Bria-IMT™ can go when combined with Incyte’s drugs. BriaCell is planning to use some of Incyte’s molecules that, like KEYTRUDA®, take the "brakes" off the immune response, for its upcoming clinical combination studies with Bria-IMT™ in advanced breast cancer.

Bria-OTS™ — Off-the-shelf personalized immunotherapy

Bria-OTS™, BriaCell’s novel immunotherapy, will be the first off-the-shelf personalized immunotherapy for advanced breast cancer. The fundamental mechanism of this treatment is to select the best pre-manufactured Bria-OTS™ immunotherapy for a patient based on the patient’s HLA type, which is determined by using a simple saliva test.

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Bria-OTS™ — Off-the-shelf personalized immunotherapy cell lines match >99% of all patients.

For reference, HLA molecules are molecules that start an immune response. If a patient, for example, is receiving an organ transplant, that patient’s HLA molecules must match those of the donor to ensure a successful procedure. "Humans have several major HLA variants that you inherit from both your mother and from your father," says Dr. Williams. "These HLA variants are expressed in most of the cells in your body."

BriaCell found that if their patients were treated with Bria-IMT™, without KEYTRUDA®, and they had a single HLA match with Bria-IMT™, tumor shrinkage was seen in 21 per cent of the patients. Importantly, tumor shrinkage was observed in 40 percent of the patients who had a double HLA match with Bria-IMT™, suggesting the importance of matching the HLA of the patient with the HLA type of the immunotherapy.

BriaCell’s scientists were then driven to see if they could genetically engineer the immunotherapy to express different HLA types – resulting in 15 HLA type specific immunotherapies, so that they could select the personalized immunotherapy for each patient based on the patient’s specific HLA type. This novel approach is expected to cover approximately 99% of the patient population with personalized immunotherapy treatments.

"We figured out a way, with 15 HLA types, to single match over 99 per cent of the population, and double match about 90 per cent of the patient population with the immunotherapy," states Dr. Williams.

“From there, once a patient’s HLA type is known, it's just a matter of shipping the matching immunotherapy cell lines overnight. This off-the-shelf process hasn't been done with other personalized cancer treatments before.”

This is exciting proof that breakthroughs can catalyze a domino effect that produces further innovations. Bria-OTS™ is expected to enter its Phase I/IIa clinical study in 2019 and hopes to make its mark as a ground-breaking treatment for advanced breast cancer patients.