Immunotherapy: the fight against cancer

Cancer consists of >100 distinct diseases that manifest in approx. 200 cell types, all with diverse genetic/mutational etiologies. Approximately 5-10% of cancers are due to genetic inheritance. The majority of cancers (70-90%) are the result of environmental risk factors including diet, smoking habit, infections such as HPV and hepatitis, and exposure to environmental factors such as UV light, ionizing radiation or water-, air-, and soil pollutants.

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From healthy cell to cancer cell

In adults, cells normally grow in size and then divide in two to produce more cells. Healthy cells live for a given amount of time before they are programmed to die by the release of chemical signals. The turnover of dying cells and newly grown cells helps keeping the body healthy by replacement of aging or damaged cells.

Upon exposure to a risk factor, healthy cells can get injured and a gene mutation takes place. Mutations can affect most, if not all, cell processes due to changing the gene structure of a cell. Healthy cells recognize most of the mutations and automatically repair them. However, if a cell has faced too many mutations, there is a chance that the cell cannot repair them any longer. As a consequence, the cell can miss the sign for its programmed death and the mutation may then be passed on to the daughter cells. This eventually leads to continuous cell growth and the cells grow out of control: the start of cancer.

The development of cancer typically occurs through the three phases of:

  1. initiation by a risk factor,
  2. promotion of cell growth to
  3. finally progress into (metastasized) cancer.

Immunotherapeutic approaches to treat cancer

With so many factors that underlie the development of cancer and so many different cancer types, how do you find the best approaches to fight cancer?

Immunotherapeutic approaches to treat cancer are rapidly making headway and it has been stated as the breakthrough of the year 2013 by Science magazine. It is based on the generally-accepted hypothesis that the immune system is the best tool humans have to fight diseases, including cancers. Cancer immunotherapy can be divided into two main categories, based on the mechanism of action of the therapy used:

  1. Active immunotherapies focus on harnessing the patient's immune system to fight cancer in vivo, through e.g. cancer vaccines. For this, the immune system should be strong enough to induce a response and mediate effector functions.
  2. Passive immunotherapies relies on treatments that have been made ex vivo, such as monoclonal antibodies, to alter the behavior of cancer cells or enhance anti-tumor activity. Adoptive cell therapy is also a form of passive immunotherapy, which involves direct transfer of (engineered) T-cells to generate anti-tumor immunity.

Active immunotherapy

Immune cell-mediated cell killing

Immuno-oncology research has focused on the use of the patient's immune system to kill cancer cells. Administration of a positive modulator of innate antitumor immunity stimulates binding of immune cells to the cancer cells. This will induce cancer cell death.

Read here how active immunotherapy works 

Passive immunotherapy

Use of monoclonal antibodies

The search for and subsequent use of monoclonal antibodies in passive immunotherapy is a so-called targeted therapy: the antibody is directed to a single and specified target on a cancer cell. Binding to the antibody induces cancer cell lysis by recruited immune cells.

Learn how antibody immunotherapy works

Passive immunotherapy

Adoptive Cell Therapy

The basis of adoptive cell therapy lies on the isolation of T-cells that are reinfused into the patient to more effectively target cancer cells. If needed, the T-cells are genetically engineered prior to reinfusion to gain avidity against cancer cell antigens. Binding of both cell types induces cancer cell lysis.

Learn how adoptive cell therapy works

References

Wu, S. et al. Substantial contribution of extrinsic risk factors to cancer development. Nature; 07 Jan 2016: Vol. 529, Issue 7584, pp 43–47

Cancer Cell Development. Canadian Cancer Society (30 Nov 2016). Retrieved from http://www.cancer.ca/en/cancer-information

Jennifer Couzin-Frankel. Cancer Immunotherapy. Science; 20 Dec 2013: Vol. 342, Issue 6165, pp. 1432-1433

Papaioannou, N.E. et al. Harnessing the immune system to improve cancer therapy. Ann Transl Med. 15 Mar 2016, Vol. 4, Issue 14, pp 261

Yang. F et al. Adoptive Cellular Therapy (ACT) for Cancer Treatment. Advances in Experimental Medicine and Biology. 31 May 2016; Vol. 909: pp 169-239