Immunotherapy Changes How We Think About Treating Cancer

Trinity oncologist say immunotherapy exploits the power of the human immune system to treat cancer

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Cancer experts from a broad cross-section of related and unrelated medical fields have united to enable the development of new therapeutics to minimize or inhibit cancer cell proliferation

According to reporting by The University Times in Ireland on November 13, 2019, ‘one of the most recent advances in cancer research is the development of immunotherapy.’

Excerpts from this article are inserted below:

More than a century old, immunotherapy was the first non-surgical treatment for cancer. 

Cancer immunotherapy has become one of the hottest areas in oncology since it was first described in 1985, and was labeled in 2013 as “breakthrough of the year” by the journal Science.

Immunotherapy exploits the power of the human immune system to treat diseases including cancer. The immune system detects cancer by recognizing protein molecules known as antigens that are uniquely expressed in cancer cells. 

Dr. Margaret Dunne, a research assistant professor, and principal investigator at the Trinity Translational Medicine Institute wrote in an email that ‘traditional therapies such as chemotherapy and radiotherapy aim to destroy tumor cells.’ 

‘However, they are not particularly tumor-specific.’

‘Whereas the goal of immunotherapy is to activate an immune response against cancer.’

However, this is tricky, says Dr. Dunne, given how complex the immune system is – not to mention how complex tumors can be. 

Dr. Dunne is responsible for having recently identified lesser-known immune cells called MAIT (mucosal-associated invariant T cell) cells that are capable of destroying malignant cells.

She explains how scientists for years were puzzled by the failure of the immune system to respond to cancer, but they now know that cancer can hide from T-cells that seek out and kill invaders.

‘Up until now, we thought that some tumors were invisible to the immune system, or that the immune response was somehow deficient, allowing tumor survival, but now we know that these processes are reversible.’

Interestingly, the Nobel prize winners (2018) James Allison and Tasuku Honjo have “fundamentally changed the way we view how cancer can be managed”. 

Their discovery presents a new principle – rather than targeting the cancer cells, proteins found on immune cells, which operated as brakes preventing the body’s natural defenses from killing cancer cells, are targeted to release the brakes, thereby unleashing the immune cells to attack cancer cells. 

These proteins are called PD-1 (programmed cell death protein 1) and CTLA-4 (Cytotoxic T- lymphocyte-associated protein 4) and are collectively termed as checkpoint proteins.

In response, checkpoint inhibitor drugs were developed that block checkpoints subject to cancer manipulation. Immune checkpoint inhibitors are approved to treat some patients with lung cancer, bladder cancer, and skin cancer, among others.

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Several other types of immunotherapies are used to treat cancers, including monoclonal antibodies, adoptive cell therapy, oncolytic immunotherapy, and cancer vaccines. 

Monoclonal antibodies are targeted antibody therapies that can directly target cancer cells or other cells/proteins that help to support tumor survival.

Dr. Jerrard Hayes, the director of Trinity’s master’s in immunotherapeutics, says that ‘monoclonal antibodies have remarkable success in the treatment of blood-borne cancer such as non-Hodgkin’s lymphomas and b-cell malignancies by recognizing and identifying antigens on the surface and then designing antibodies against those antigens and then engaging the immune system, usually by natural killer cells.’

Adoptive cell therapy is a treatment that uses immune cells taken from a tumor and engineers them to be more capable of targeting and destroying cancer cells. One type of adoptive cell therapy is chimeric antigen receptor T cells (CAR-T cells).

Regardless of the outcome of immunotherapy, patients are still at risk of suffering side effects. 

As well as the general risk of contracting fever and nausea, says Dr. Kingston Mills, professor of experimental immunology in Trinity’s School of Biochemistry and Immunology.

In the case of immune checkpoint inhibitors, the main side effect is the development of immune-mediated diseases, such as autoimmune disease.

Dr. Mills explains that this occurs because you are “allowing the immune system to be uncontrolled, and an uncontrolled immune system can result in immune response attacking itself and that’s what autoimmunity is.’ 

‘So, it’s not surprising that patients treated with immune checkpoint inhibitors will develop an autoimmune disease, such as colitis, a type of gut inflammation.’

Despite the lack of certainty concerning its effectiveness and the possibility of side effects, the future looks bright and exciting for the field of cancer immunotherapy. 

With hundreds of immunotherapies in clinical trials and research testing of immunotherapy combined with standard treatment well underway. 

Dr. Dunne concludes saying ‘The future holds a lot of promise, but there is still a lot for us to learn.’

This article was written by Khadija Haouit, a Contributing Writer. The University Times is Ireland’s largest student newspaper and is the current Student Publication of the Year, an award which it has won four years running. 

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