Cancer Ward was first published in 1967. Its political implications have expired, but the emotional trauma of the terminally ill cancer patients continues still, worldwide. Pulitzer Prize winner (2011) The Emperor of All Maladies resonates with the very same despair- If only ....... there could be a cure! 4th of February happens to be World Cancer Day. Most appropriate day for us to examine the latest in the treatment of cancer. Have we hit upon anything new?
Recent issues of both Nature and Science are unanimous in hailing Immunotherapy as a paradigm shift in the treatment of cancer. What is so special about immunotherapy, that it tops the list of Newsbreakers of 2013? The fundamental difference is that till now all treatments, (whether the the hot ray or cold knife as Mukherjee puts it), focused on the cancerous tissue whereas the new mindset aims to boost, equip and train body's immune system to stand up against cancer cells. The thought process had begun almost 125 years ago, when William Coley, a surgeon at the New York Cancer Hospital ( now part of Memorial Sloane Kettering Cancer Center), accidentally came across a cancer patient whose tumor had miraculously disappeared after a bacterial infection. Coley was excited and interested. He was correct in assuming that the infection was instrumental in the disappearance of cancerous growth and quickly began a series of tests on other cancer patients. Coley deliberately infected them with a similar bacterial concoction. Though proved successful, this line of treatment was soon discontinued for two reasons. One: clean and quick radiation therapy entered the stage in early 1900s, second: standardized and reproducible procedures for infection therapy (actually vaccination therapy) were not yet in place, bacterial concoction had to be adjusted to suit each patient. Hundred plus years later doctors and scientists dug up Coley's records and came to the conclusion that the bacterial infection might have rejuvenated cancer patient's immune system somehow. And that is one of the anchoring points of modern day immunotherapy : boost, equip and train body's immune system to attack cancer cells. While there are several drugs to ensure the general robustness and readiness of the immune system, how to train and equip them to attack the cancerous growth?
The most remarkable feature about vertebrate immune system is adaptability. And it is this feature that is being exploited extensively in immunotherapy. Immune system, body's defense force, comprises of white blood cells (also called leucocytes). They are indeed organized as an army with several cadres entrusted with very specific and exclusive responsibilities. Alert watchmen, the dendritic cells (DC) are ever on the patrol, always on the look out for foreign intruders, enemies ( scientific term Antigen). If they spot anything new they will grab a sample and carry it to the soldiers' training center. Soldiers in training, the immature T cells, will puff and sniff at the foreign body and recognize it as the enemy . Memory T cells will lock up the information in their data bank for present and future use; helper T cells will produce weapons (antibodies against the antigen), and killer T cells will go all out for the enemy. Regulatory T cells meanwhile will take care of the supply logistics. But here is the catch - the whole system is geared to work against aliens. Cell division is a natural process, only difference is that in cancerous tissues this process is unstoppable. When the enemy is unidentifiable how can a defense strategy be set up ?
Scientists are trying out various tricks. One approach is to empower the patrollers, the dendritic cells, to recognize the cancerous cells. Immature DCs are taken out of the patient's blood, differentiate and activate them in culture, load them with tumor specific antigens and then inject the cells back into the patient" explains immunologist Karolinska Palucka. The vaccine Provenge for the treatment of prostate cancer falls under this category. Another approach is to nudge the killer T cells. Immune system has a number of checks and balances to ensure that it doesn't turn suicidal, means it doesn't attack body's own cells. Several oncologists from various research hospitals individually and collectively observed that tinkering with these checks and balances often proved helpful. Dr James Allison noticed that a protein identified as CTLA-4 is one such check point protein. It doesn't allow the killer T cell to demonstrate its full capability. Allison argued that if he can turn off CTLA-4, the killer T cell would realize its full potential. Could it then be coaxed to attack the tumor cell?. Allison used a specially designed protein, (a monoclonal antibody to be precise), in mouse models for melanoma (skin cancer) and got very successful results. After decades of intense studies and trials, Bristol-Myers-Squibb finally received US FDA approval in 2011. Currently in the market as Ipilimumab for treatment of melanoma , its price tag is a whopping US$120,000 for a course and it isn't clear minimum how many courses one needs.
Tinkering with the immune system may not be without risks. But as Couzin-Frankel concludes : "One book has closed, and a new one opened. How it will end is anyone's guess"
1. Cancer Ward : Alexander Solzhenitsyn
2. Emperor of All Maladies- A Biography of Cancer : S Mukherjee
3. Cancer Immunotherapy Nature 504,(7480). ppS1-S1719/26 December 2013
2. Emperor of All Maladies- A Biography of Cancer : S Mukherjee
3. Cancer Immunotherapy Nature 504,(7480). ppS1-S1719/26 December 2013
4. Cancer Immunotherapy Science 342, p1432-1433, 20th Dec 2013
