The title that the cancer specialist, Dr Siddhartha Mukherjee chose for his Pulitzer-prize winner book on cancer was “The Emperor of All Maladies.” It signifies both the awe and a sportsman-like admiration of the challenge posed by the opponent, cancer. Earlier in 1971, President Richard Nixon of the US, on a similar vein, declared a “war on cancer,” with a federal funding of $1.4 billion. And over these 47 years, the US National Cancer Institute alone has spent $90 billion on the war on cancer. We are yet to win.
Each year, 1.73 million new cancer cases are reported in the US, with apparently one cancer death every 20 minutes. In India, it is 2.5 million people, with one death every 8 minutes. It is thus urgent and vital that solutions be found for this deadly disease, which has been with us since the dawn of civilisation.
Cancer occurs when an otherwise healthy cell is damaged, leading to uncontrolled growth, affecting the health of the body. Damage can occur either because of inborn or inherited errors in one or more genes affecting the cell, or due to lifestyle and environmental factors. While normal cells are programmed to multiply and grow to a certain size and stay so, cancer cells, whose DNA is mutated by such damage, go on rampant growth leading to tumours. The cancer specialist removes these errant cancer cells and tumour by medication or surgery. But the big challenge is not the first treatment alone, but that it should not recur and/or metastasise (move to and affect other parts of the body). The fight against cancer is thus to uproot the cause of the damage once and for all.
Immunity
It is here that we turn to the in-built defense mechanisms in the body. These are through the immune system, which is a complex network of cells, tissues and the molecules they make to help in fighting infections and other diseases, including cancer. White blood cells play the main role here. In particular, there is the group of cells called B-lymphocytes which recognise the shape of the molecules in the invader, and make proteins called antibodies which lock on to the invader and removes it. (Importantly, this shape is ‘remembered’ so that when a fresh attack by this same invader occurs, B cells are prepared!) Another set called T cells release chemicals that push the invading cells to commit suicide. In this process, these T-killer cells are aided by a group called T-helper cells. In addition, there is another group called dendritic cells which help activate both the B- cells and T-killer cells, enabling them to respond to specific threats.
Each cell has on its surface a little marker, a small molecular ID- card or a biometric, called an antigen. These are small molecular fragments found on the cell surface. Antigens in the normal cells of the body are recognized as “self” by the immune system of the body and left alone. But when “foreign” cells such as those of an invading microbe or virus enter the system, their ‘non-self’ antigens are detected, attacked and thrown out of the body by the B and T lymphocytes.
This is also the basis of vaccines. In a vaccine, we introduce the disease- causing germs (either in the dead from or highly- disabled “live” form) into the body. This causes the immune system to recognise the “non-self” foreign antigen, grab it (using the antibody proteins) and throw it out of the body. Plus, the immune system ‘remembers’ this non-self antigen and when the invader comes again, has the B cells make antibodies against it and remove it from the system, thus offering protection for a long time. This is the basis behind vaccination against many diseases, including cancer-causing viruses such as human papilloma virus (HPV) and the hepatitis B and C viruses.
Once bitten, twice prepared
How is this relevant to other forms of cancer? Cancer cells too have antigens on their surface. These form the cancer-associated antigens, including some that have not been seen previously by the body’s immune system. These are called neo-antigens. They are foreign to the body, and come from the invader.
In the current excitement on the cure of the cancer, this idea of using our immune system and make an anti-cancer vaccine is on the high table. This is not a preventive vaccine (as the HPV or hepatitis vaccines are) but a therapeutic (or treatment) vaccine. Here, the doctor first treats the cancer by existing methods. In order that it does not recur, nor metastasise, he/she then takes a piece of the cancer tissue from the patient, and has the neo-antigens identified. Next, he/she works with a group of scientists who use computer methods to check which fragment will trigger the patient’s immune system best to fight the cancer cells. The so-chosen neo-antigen is used to make the vaccine, and once the vaccine is made, use it on the patients to protect them from further recurrence of the illness and thus get rid of the cancer, hopefully forever.
Some cancer vaccines are already in the market; for example, HER2 against breast cancer, Provenge against prostate cancer, and T-VEC against melanoma. Increasingly though, some researchers want to read the patient’s genome, sequence the DNA or RNA of the tumor there, identify the mutations therein and make a specially constructed ‘personalised’ vaccine for the individual. The emperor may hit and maul. But now that we are adopting the Boys Scouts slogan, “Be Prepared”, will his days be numbered?
dbala@lvpei.org
