Immunotherapy is a treatment approach that uses a body’s natural immune system to control or eliminate cancer.

The immune system consists of cells, tissues and organs that work together to defend against various infections and disease, such as the flu, by rooting out and attacking foreign cells, including abnormal cells that cause cancer. But cancer cells sometimes look too much like normal cells for the immune system to recognize them as foreign, and sometimes cancer cells can keep the immune system from working properly. Immunotherapy aims to assist in triggering an effective immune system response.

There are many different types of immunotherapy used to treat cancer, and all have the goal of either restoring the immune system’s ability to attack cancer cells, or identifying and destroying cancer cells specifically.

In 2016, the Conconi Family Immunotherapy Lab, located at BC Cancer’s Deeley Research Centre in Victoria, opened to become the hub of custom immunotherapy treatment production for cancer patients across B.C. Research teams at the lab are currently developing two promising forms of Adoptive T Cell Therapy for lymphoma and leukemia: CAR-T cells and oncogene-targeted T cells.

Cell therapy seeks to trigger immune response

Immune cells that directly attack cancer are a type of white blood cell called T lymphocytes.  Sometimes they are ineffective, but recent clinical research has shown that it’s possible to boost their effectiveness by modifying the cells to add a specific type of molecule that recognizes and seeks out cancer.

The process involves isolating a sample of a person’s T lymphocytes from their blood, identifying the T cells already attempting to destroy cancer, modifying the cells in a lab, and then re-administering them back to the same person. This is a type of Adoptive Cell Therapy (ACT).

The genetic modification that happens in the lab involves introducing an extra gene into the T cells that carries instructions for a new component called a Chimeric Antigen Receptor (CAR). It is “chimeric” because it contains different sub-components fused together, and it is an “antigen receptor” because it recognizes specific features, or antigens, on the surface of tumour cells. (Antigens are molecules that trigger the immune system. Germs and cancer cells have antigens on their surface.)

The CAR-carrying designer genes are a powerful way to give T cells the ability to recognize and destroy cancer cells in a very precise manner. The first generation of CAR-T cells recognize a molecule called CD19, which is often found with leukemia and lymphoma. The use of modified CD19 CAR-T cells has achieved great clinical success at centres around the world, showing high success rates of eradicating cancer cells to the point where they can no longer be detected in studies of some patients with certain forms of advanced disease.

Researchers at BC Cancer are currently working to develop a CD19 CAR-T cell program in B.C. that can be expanded to other centres across Canada. Genetic engineering of T cells is a complex process that requires specialized equipment and expertise. Working with researchers in Ottawa, the BC Cancer team is designing innovative approaches to simplify the engineering process so this life-saving treatment can be made affordable and accessible to more patients.

A CAR-T cell trial at BC Cancer with people who have relapsed Acute Lymphoblastic Leukemia (ALL) is set to begin in 2019. The BC Cancer team is also developing exciting new ways to extend CAR-T cell therapy to other types of cancer.

Dr Julie Nielsen

 

 

“The power and specificity of the immune system makes immunotherapy a very promising approach.”

- Dr. Julie Nielsen – researcher at the Deeley Research Centre, BC Cancer Vancouver Island Centre

Research providing targeted cell therapy potential to other types of cancer

Despite the success of certain trails of CD19 CAR-T cells, currently they can only be used to treat lymphoma and leukemia that express CD19. So BC Cancer’s research teams are also developing a second approach to Adoptive Cell Therapy that can be applied more widely. Patients will be infused with different T cells, called oncogene-targeted T cells, which recognize mutations driving tumour growth.

Cancer is caused by mutations in a core set of genes (referred to as “oncogenes”) that control the growth of cells. Although most oncogenes have been known to science for decades, many have proven very difficult to target with drugs.

An additional challenge is that the “culprit” oncogenes are different in each patient, but about 100 common oncogenes have been identified in lymphoma, providing a shortlist of targets for treatment.

BC Cancer researchers in Victoria, led by Dr. Julie Nielsen, have shown that many lymphoma patients have T cells in their blood that can detect the mutant oncogenes in their cancer cells. These T cells are found in very low numbers in patients, which likely explains why they are unable to eliminate the cancer cells on their own. But the cells can be isolated from blood samples and expanded to very large numbers (tens of billions) in the lab. This presents the possibility of isolating the T cells, expanding their numbers, then reintroducing them, giving infusions of oncogene-targeted T cells that can seek and destroy tumour cells throughout the body. (Read more in Dr. Nielsen's blog post)

An oncogene-targeted T cell trial in relapsed follicular lymphoma and relapsed diffuse large B-cell lymphoma is set to begin at BC Cancer in 2019.

In the past year, BC Cancer teams have also developed techniques that make it possible to identify a greater number and variety of tumour-specific T cells, and are currently testing strategies to generate T cells with greater activity. They are also working to separate the most active T cells from those that are less likely to be effective. To learn more about BC Cancer’s ongoing clinical trials speak to your oncologist.

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