As Covid-19 ravages the world through 2020 and into 2021, the race is on among nations to vaccinate their populations against this scourge and end the pandemic. 

The record time of less than a year that scientists took to invent, test and deploy effective vaccines against Covid-19 is an amazing story that will be told and retold for generations. As of June 2021, Covid-19 had claimed the lives of some four million people worldwide.

Meanwhile, another health scourge has claimed 10 million lives worldwide in 2020 without drawing any such dramatic attention to itself. Cancer.

Imagine if we had a vaccine that would make us immune to cancer and end this health scourge as well. Wouldn’t that be wonderful? Too good to be true, you said? This idea is not as preposterous as you think.

Unbeknownst to most outside the healthcare industry, oncologists have been toiling for more than 10 years to come out with vaccines that will conquer cancer.

The relatively new technology of messenger ribonucleic acid (mRNA) vaccine behind the success of several Covid-19 vaccines has, in fact, been used in these cancer vaccine experiments for many years to try and educate the human immune system to recognise abnormal protein on the surface of cancer cells.

Cancer vaccines are a potentially important part of the puzzle of immunotherapy in cancer, that is, harnessing the immune system to destroy cancer.

But alas! The rapid success of Covid-19 vaccines was not replicated in the field of cancer. The only cancer vaccine ever to be approved by the Food and Drug Administration of the United States was one designed against prostate cancer known as sipuleucel-T.

Sadly, the effectiveness of this vaccine was so low that it has largely been abandoned by the oncology community along some forgotten byway.   

However, while efforts to develop an anti-cancer vaccine stumbled, other technologies harnessing the power of the immune system against cancer are coming of age.

One of the most successful approaches in cancer immunotherapy has been the stripping of the “cloak of invisibility” of cancer cells.

The immune system has the ability to recognise abnormal cells in the body, such as cancer cells, and to take them out. At least in theory.

However, cancer cells are like wolves in sheep's clothing thus fooling the immune system to take them for sheep and not attack.

This “sheep's clothing” or “cloak of invisibility” is known as PD-L1. Oncologists now have at their disposal several antibodies designed to strip the sheep's clothing off the wolves’ backs, known as anti-PD1/L1 immune checkpoint inhibitors.

These are actively in use in Singapore and many parts of the world against a wide spectrum of cancers such as lung cancer, breast cancer, kidney cancer and liver cancer.

These anti-PD1/L1 antibodies can, on occasions, successfully control cancer in an advanced stage for a very extended period lasting years, a phenomenon not commonly seen in treatment outcomes using conventional chemotherapy. The side effect profile is also usually gentler than that associated with chemotherapy.

Another approach that has seen success is the creation of “X-men” against cancer.

In the Hollywood blockbuster movie “X-men”, mutant super heroes engaged in mortal combat with mutant villains who threatened the peace of the world.

A similar scenario of good mutant immune cells against evil mutant cancer cells can be re-created in the body.

To achieve this, the white blood cells (known as lymphocytes) of the cancer patient’s immune system are extracted and genetically modified to create a mutant with superpowers against cancer.

These mutant cells have special receptors on their surface to be able to recognise cancer cells and launch an attack.

In medical jargon, these are chimeric antigen receptor T-lymphocytes, or CAR-T in short. These mutant lymphocytes are cloned to expand their numbers and this newly minted squad of crack troops against cancer are returned to the cancer patient’s body through the bloodstream.

However, when these mutant white blood cells battle the cancer cells in the body, not unlike the fierce fighting scenes in the movie “X-men”, they kick up quite a storm and much collateral damage can happen.

Scientifically, this collateral damage is termed a “cytokine storm” and results from the release, by the mutated lymphocytes, of molecules triggering severe inflammation in the body that can sometimes be life-threatening.

CAR-T cell therapy has been used with good results against cancers of the blood cells such as leukaemia and lymphoma, often grouped together as “liquid cancers”.

The use in cancers affecting solid organs such as the breast, lung or liver, that is, “solid cancers”, has been met with considerably less success.

Finally, let’s return to the Gordian Knot of cancer vaccines.

Oncologists have not entirely given up hope on developing a successful vaccine against cancer.

There is a vital difference between an anti-viral vaccine and an anti-cancer vaccine.

In a viral pandemic, people are generally infected by an identical virus.

Or, if there are variants of the virus, there would usually be no more than a handful.

While developing a Covid-19 within a year is a big challenge, the task is simplified by the vaccine being largely a one-size-fits all.

The genome of cancer cells, on the other hand, incorporate the unique genetic makeup of the individual patient with the mutated cancer genes.

Cancer cells in each patient are therefore unique and genetically distinct. Scientists now believe that the sword that will cut the Gordian Knot lies in developing patient-specific vaccines, a unique vaccine for each patient.

How’s that for a challenge?

ABOUT THE AUTHOR:

Dr Wong Seng Weng is medical director and consultant medical oncologist at The Cancer Centre (Singapore Medical Group) at Paragon Medical and Mount Elizabeth Novena Specialist Centre.