Immunotherapy is counterintelligence against cancer

by Dr Ang Peng Tiam, medical director and senior consultant, medical oncology, Parkway
Cancer Centre.

Immunotherapy is a buzzword currently resounding in research centres and
universities alike. It refers to a treatment that lets us tear away the disguise
cancer cells use to hide from our bodies’ natural defences, and then to use the
immune system to heal ourselves. One way to think of it is as a
counterintelligence operation in our bodies, where we unmask and eliminate
the enemies in our midst.

Oncologists have already been deploying new treatments along these lines in
recent years. A new class of immunotherapy agents called programmed cell
death protein-1 inhibitors (PD-1 inhibitors), is of particular interest.
In the mid-1990s, I, along with two of my colleagues at Singapore General
Hospital, began some new research by asking whether cancer occurred in
patients because their immune system was impaired. We found that there was
no difference, in this regard, between healthy people and those who had
developed cancer, so we then wondered how it was that these cancer cells
could escape detection by our body’s immune system.

Our theory was that cancer cells could camouflage themselves somehow. They
must have been able to hide so that the immune system could not detect and
destroy them.

To test the hypothesis, we asked patients with superficial, easily accessible
tumours for consent to inject foreign genetic material directly into their cancers.
This genetic material was meant to let the tumours present themselves as foreign
to the immune system—as coming from outside the patient’s body. And much
to our delight, we saw some of these tumours shrink and even disappear.
This made us more certain that cancers did not flourish because of a deficiency
in the immune system, but rather because they could hide or protect
themselves from competent immunity.

Now fast-forward to the present decade. Researchers have found that the Tcells
in our immune system have a surface receptor called programmed cell
death protein-1 (PD-1). Many cancer cells can produce a protein, called a
ligand, that blocks this receptor and stops the T-cells from attacking and killing
them. Two pharmaceutical companies have now come up with antibodies that
prevent this blockage, freeing the activated T-cells to do their job of killing the
cancer cells. The two currently available immunotherapy drugs based on this
principle are pembrolizumab (Keytruda) and nivolumab (Opdivo).

The results of studies using immunotherapy have been nothing short of amazing.
In one study, code-named CheckMate-057, advanced lung cancer patients
who had been previously treated with first-line chemotherapy were randomly
assigned to either a control group that would receive a standard
chemotherapy, docetaxel, or to an experimental group that would be treated
with nivolumab, an immunotherapy.

Patients who received nivolumab lived longer than those in the control group,
seeing their risk of death fall. One-year odds of survival were 51% for the
nivolumab group, compared to 39% for the docetaxel group. Such novel agents
have also been shown to be effective in treating melanoma, colon cancer and
malignant lymphoma.

Excitement over the use of immunotherapy remains high. The recent
announcement that former United States president Jimmy Carter achieved
cancer remission after treatment with pembrolizumab has heightened interest.
In his last state of the Union Address, the current president, Barack Obama, has
declared an American commitment to end cancer “once and for all”. There
are now more resources and people committed to cancer research than ever
before. But the promises that come with new discoveries must be tempered with
caution: disappointingly, treatments that are successful in clinical trials may
show different results in the real world.

Nonetheless, we are discovering more and more that immunotherapy can help
the body heal itself, and that is a great cause for hope.

This article is provided courtesy of The Economist.  Join them at the War on Cancer, a forum of  distinguished world leaders in healthcare.