Science on the Attack: Cancer Immunotherapy

As a diversion from my regular blog posts examining how science is under attack, occasional posts such as this one will showcase examples of science nevertheless on the attack – to illustrate the power of the scientific method in tackling knotty problems, even when the discipline itself is under siege. This will exclude technology, which has always thrived. The first example is from the field of medicine: cancer immunotherapy.

Cancer is a vexing disease, in fact a slew of different diseases, in which abnormal cells proliferate uncontrollably and can spread to healthy organs and tissues. It’s one of the leading causes of death worldwide, especially in high-income countries. Each type of cancer, such as breast, lung or prostate, has as many as 10 different sub-types, vastly complicating efforts to conquer the disease.

Although the role of the body’s immune system is to detect and destroy abnormal cells, as well as invaders like foreign bacteria and viruses, cancer can evade the immune system through several mechanisms that shut down the immune response.

One mechanism involves the immune system deploying T-cells – a type of white blood cell – to recognize abnormal cells. It does this by looking for flags or protein fragments called antigens displayed on the cell surface that signal the cell’s identity. The T-cells, sometimes called the warriors of the immune system, identify and then kill the offending cells.

But the problem is that cancer cells can avoid annihilation by deactivating a switch on the T-cell known as an immune checkpoint, the purpose of which is to prevent T-cells from becoming over zealous and generating too powerful an immune response. Switching off the checkpoint altogether takes the T-cell out of the action and allows the cancer to grow. The breakthrough of cancer immunotherapy was in discovering drugs that can act as checkpoint inhibitors, which keep the checkpoint activated or switched on at all times and therefore enable the immune system to do its job in attacking the cancerous cells.

However, such a discovery wasn’t an easy task. Attempts to harness the immune system to fight cancer go back over 100 years, but none of these attempts worked successfully on a consistent basis. The only options available to cancer patients were from the standard regimen of surgery, chemotherapy, radiation and hormonal treatments.

In what the British Society for Immunology described as “one of the most extraordinary breakthroughs in modern medicine,” researchers James P. Allison and Tasuku Honjo were awarded the 2018 Nobel Prize in Physiology or Medicine for their discoveries of different checkpoint inhibitor drugs – discoveries that represented the culmination of over a decade’s painstaking laboratory work. Allison explored one type of checkpoint inhibitor (known as CTLA-4), Honjo another one (known as PD-1).

Early clinical tests of both types of inhibitor showed spectacular results. In several patients with advanced melanoma, an aggressive type of skin cancer, the cancer completely disappeared when treated with a drug based on Allison’s research. In patients with other types of cancer such as lung cancer, renal cancer and lymphoma, treatment with a drug based on Honjo’s research resulted in long-term remission, and may have even cured metastatic cancer – previously not considered treatable.

Yet despite this initial promise, it’s been found that checkpoint inhibitor immunotherapy is effective for only a small portion of cancer patients: genetic differences are no doubt at play. States Dr. Roy Herbst, chief of medical oncology at Yale Medicine, “The sad truth about immunotherapy treatment in lung cancer is that it shrinks tumors in only about one or two out of 10 patients.” More research and possibly drug combinations will be needed, Dr. Herbst says, to extend the revolutionary new treatment to more patients.

Another downside is possible side effects from immune checkpoint drugs, caused by overstimulation of the immune system and consequent autoimmune reactions in which the immune system attacks normal, healthy tissue. But such reactions are usually manageable and not life-threatening.

Cancer immunotherapy is but one of many striking recent advances in the medical field, illustrating how the biomedical sciences can be on the attack even as they come under assault, especially from medical malfeasance in the form of irreproducibility and fraud.

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