Every day, an average of 78 Canadian women are diagnosed with breast cancer and an average of 15 women die from the disease¹. Cancer research continues to lead to new and improved treatments that save lives; however, some types of cancer still remain particularly challenging to treat. One such aggressive tough-to-treat type is called triple-negative breast cancer, which accounts for approximately 15 per cent of breast cancer cases. A team of GlycoNet researchers has developed specialized antibodies that could help the immune system fight triple-negative breast cancer more effectively. 

When it comes to cancer treatment, most people have probably heard of radiotherapy or chemotherapy—the use of radiation or chemical substances—to kill cancer cells that cannot be removed via surgery. Immunotherapy may sound less familiar—this treatment essentially involves helping your immune system recognize and fight cancer. A huge benefit of leveraging the immune system is that it can reach anywhere in the body.

“The problem with immunotherapy is it doesn’t always work,” says Dr. Yves St-Pierre, GlycoNet researcher and professor at the Institut National de la Recherche Scientifique (INRS). “When it works, it’s fantastic, but it works in about only 20 per cent of cases. So our job as immunologists working on cancer is really to increase that percentage.”

Cancer cells are tricky to tackle—they can hide, mutate, and often respond to attacks from immune cells by producing their own army of proteins that neutralize or kill immune cells. Dr. St-Pierre has been leading a multidisciplinary team to better understand the structure of these proteins and how to target and prevent them from killing immune cells.

“We are interested by one group of these, a family of proteins that are produced by cancer cells called galectins—proteins that bind sugar,” explains Dr. St-Pierre. “It’s a family with many members and most of these members are able to kill immune cells.”

“If we can neutralize these galectins, then we’re going to help the immune cells—we’re going to neutralize one of the major signals that kills the immune cells.”

One of the normal roles of galectins in the body is to help regulate the immune system. For example, when there is a need to calm the body’s immune response, other cells will release galectins at low levels to communicate with immune cells and tell them that their work is done. Meanwhile, cancer cells produce a high level of galectins that overwhelms the immune system and results in killing or deactivating the immune cells.

A promising galectin inhibitor that the research team has been developing involves a type of antibody found in llamas and camels—members of the camelid family. These camelid antibodies are much smaller than human antibodies and have earned the name “nanobodies.” These nanobodies can get into places that regular human antibodies cannot due to their size and they can be used to design drugs that target specific galectins associated with different types of cancer. Targeting only the relevant galectins is important to avoid potentially causing adverse effects.

The team’s proof of concept is a nanobody tailored to target galectin-7, the major galectin produced by triple-negative breast cancer. Dr. St-Pierre brings expertise in immunology and cancer to the project, and is collaborating with Drs. David Chatenet and Nicolas Doucet, GlycoNet researchers and professors at INRS, who specialize in understanding the behaviour and structure of nanobodies, respectively.

Dr. St-Pierre and his team are now carrying out preclinical trials with this particular nanobody that targets galectin-7.

Other potential benefits and applications 

Dr. St-Pierre’s team also plans to explore how nanobodies can be used in imaging to help detect tumours. For instance, nanobodies can be tagged with particles called radioisotopes for diagnostic purposes.

“If the patient has even a small tumour that overproduces galectin-7 for instance, then when we inject a nanobody that has a radioisotope on it, we will find a hot spot and then we can go investigate,” says Dr. St-Pierre.

“You can get some radioisotopes that will not only find the tumour and allow you to see it via the scan, but at the same time will kill the cancer cells,” adds Dr. St-Pierre. “So this is what we call a theranostic—you do the diagnosis and the therapy with the same drug.”

Producing regular antibodies traditionally used in immunotherapy is complicated and costly. Nanobodies are much cheaper to produce in a lab, so not only could their usage improve the success rate of immunotherapy but it could also reduce the cost of immunotherapy.

Although triple-negative breast cancer is the team’s current project focus for preclinical trials, the team has developed approximately 30 different nanobodies to target different galectins, which could potentially be applied to treating other types of cancer.

The research is funded by GlycoNet, CQDM and industry partners, Canadian Institutes of Health Research (CIHR), and scholarships provided by Fonds de recherche du Québec – Santé (FRQS).

¹Canadian Cancer Society. (May 2022). Breast Cancer Statistics. Retrieved from https://cancer.ca/en/cancer-information/cancer-types/breast/statistics