FIGHTING CANCER FROM THE INSIDE: IMMUNO-ONCOLOGY BREAKTHROUGHS

"I had a desire to do something meaningful." This was biologist Laura Helming’s answer when asked about her decision to dedicate herself to the field of immuno-oncology. Her path toward this branch of medicine, which uses the body's own immune system to fight cancer cells, involved a series of intermediate stages. When Helming studied biology as a student, she was particularly interested in genetics and infectious diseases. As the immune system and infectious diseases are inherently linked, the decision to pursue immunology was a logical next step.

After working in the area for several years, Helming was given the chance in 2013 to work for Merck KGaA, Darmstadt, Germany in the field of immuno-oncology. She refers to working at the intersection of immunology and oncology and exploring new therapies fight cancer as an “incredible opportunity.”

“It's a privilege to be able to work as a scientist in this field,” says Helming.

In 2012, Ed Quinn was diagnosed with cancer. In his fight against the disease, he never gave up hope.

Nine months. If things go well, a year. This was how much time Ed Quinn was told he had to live. Though his world collapsed, his family stayed positive. When he saw no way out, they gave him strength and helped him to get back on his feet.    

After grueling rounds of radiotherapy and chemotherapy, Ed is a survivor. He achieved remission, he believes not only because of a medical treatment, but because of his strong will. While his cancer returned, he knows how important it is for the recovery to never lose hope. Quinn shares his personal story in the video below. 

Immuno-oncology as an idea is nothing new. But it wasn’t until 2011 that a clinical milestone was reached with the approval of the first immuno-oncological drug for the treatment of cancer.

Laura Helming is working on the ”immune” part of the term ”immuno-oncology.” Her entry in this field came at an auspicious time. Certainly, the idea of immuno-oncology per se is not new. Bacteria were being injected directly into tumor tissue in the nineteenth century in order to stimulate the immune system to fight tumor cells. Real breakthroughs in this field, however, have only been witnessed in the past few years.

An important milestone was achieved in 2011 when an immuno-oncology drug was approved to fight advanced malignant melanoma. (1) The success of this new treatment for melanoma – against which different kinds of therapies had previously shown limited effect – was significant. Since then, the many drugs that have emerged from the combination of immunology and oncology have led some experts to deem immuno-oncology a ”quantum leap” in cancer therapy. Helming is more cautious, and yet ”very hopeful" she will play a part in helping to deliver on the promise of immunotherapies for patients fighting cancer.    

Immuno-oncological agents can have varying effects on the immune system. However, not all cancers are equally suited to treatment with these new medications.

The immuno-modulatory effect of compounds – i.e. their impact on the immune system – can take place in a variety of ways. Immuno-oncology agents, for instance, can directly activate the immune system to fight cancer cells. (2) Another important approach is to deactivate potential ”brakes” to the immune system that prevent it from attacking the cancer cells. (3) An important target are cytotoxic T cells, whose primary role within the immune system is to identify diseased cells and destroy them. However, T cell function can be impaired within cancer and as a result, the T cells do not attack the cancer. The tumor cells, as a consequence, continue to divide and the tumor grows. (2) Several immuno-oncology compounds influence this process by preventing inhibitory influences on T cells.

Not every cancer or every patient, though, is equally suited to these new drugs. In short: Immuno-oncology may require an exact diagnosis of the tumor tissue to enable the treatment of those patients who will benefit from an immuno-oncology drug.    

The history of immuno-oncology is one of gradual progress towards a single goal: developing life-saving treatments that mobilize the body’s own immune system to fight cancer and prolong life.

1867

The birth of immuno-oncology: Bonn surgeon Wilhelm Busch notes in a patient that her tumor has regressed after an infection. (4)

1891

William B. Coley, M.D. at Memorial Hospital in New York, first attempts immune-modulating therapy for cancer with the inoculation of a sarcoma patient with cultures of erysipelas. (5)

1909

Paul Ehrlich proposes that the immune system usually suppresses tumor formation, a concept that becomes known as the “immune surveillance” hypothesis. (5)

1941

Albert Coons develops the fluorescent antibody technique, which enables the localization and identification of antigens. (5)

1948

Astrid Fagraeus demonstrates antibody production by plasma cells, later to be identified as the products of B lymphocytes. (5)  

1974

César Milstein discovers the principle for the production of monoclonal antibodies, which can selectively fight tumor cells, while sparing healthy cells. (6)

1997

The first monoclonal antibody is approved to treat cancer. (5)

2011

The first cancer immune therapy is approved for the treatment of malignant melanoma. (1)

While previously only the tumor itself or its cells were examined, the research focus is now being directed ever more at the so-called tumor microenvironment. This tumor microenvironment contains a complex network of different cells – including immune cells, which affect the growth of the tumor through their interactions.

Laura Helming sees important future research in the study of these regulatory processes. As the tumor environment could have an influence on the success or failure of a therapy, new research in this area may help to improve cancer treatments in the future. This may also lead to the discovery of new ways of influencing tumor growth via the immune system.    

The development of a new immuno-oncology drug requires the expertise of many different disciplines. In the area where Laura Helming is active, the so-called preclinical studies, biologists work alongside pharmacists, biotechnologists, chemists, and others.

In contrast to the clinical development phase of a drug, new compounds are tested in preclinical trials on specific cell and tissue cultures, not on human beings. Laura Helming however, does not work in a laboratory anymore, but at a desk. Her workday therefore differs little from a normal day at the office, and she is mainly preoccupied as a scientist with the scientific data on the examined compounds. What experiments will still need to be carried out to obtain solid data on a new agent? Are the available data sufficient for continuing to work with the compounds? How can the development process be expedited?

Not only are questions like these discussed within the team, but the answers could end up forming the basis for a new immuno-oncology agent.

Even so, as with ”normal” drugs, it can take years before its possible use as a medication. What is more, very few of the many initially promising compounds will become a possible new treatment to fight cancer.    

1. Cancer Research Institute, Melanoma, last revised October 2015, retrieved May 20, 2016 from cancerresearch.org

2. Kirkwood, J.M., Butterfield, L.H., Tarhini, A.A., Zarour, H., Kalinski, P., and Ferrone, S. Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012; 62: 309–335

3. Weber, J. S., Immuno-oncology Comes of Age – Introduction, In: Seminars in Oncology, 2014, 41:S1-S2

4. Cancer Research Institute, Sarcoma, last revised May 2016, retrieved May 20, 2016 from cancerresearch.org

5. Cancer Research Insitute, Timeline of Progress, retrieved May 20, 2016 from cancerresearch.org

6. The American Association of Immunologists, César Milstein, Ph.D. (1927–2002), retrieved May 20, 2016 from aai.org

7. Stewart, B., and Wild, C. P. Wild, World Cancer Report 2014, retrieved May 20, 2016 from iarc.fr

8. Genetic Engineering & Biotechnology News, last revised February 1, 2016, retrieved May 20, 2016 from genengnews.com