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That was in 1891. Zola, an Italian immigrant living in New York – his first name was lost because of the dawn of time – had a malignant tumor the size of an egg on his neck that was almost obstructing his feed pipe. At that time, the only way to treat cancer was surgery. Zola went to see Dr. William Coley, head of the bone sarcoma unit at Memorial Hospital in New York, USA.
The first cancer patient of Dr. Coley, an 18-year-old girl, had just lost her fight against cancer, leaving him distraught, but determined to find a way to stop the disease. He had consulted the archives of the hospital and had discovered cases of patients completely cured of cancer after contracting a strep infection. This gave him the idea that a bacterial infection can perhaps strengthen the body's defense mechanism, thus helping it to fight against cancer. To find out, he created a mixture of bacteria that he would call Coley's toxin or Coley's fluid. Following the path indicated by Edward Jenner and Louis Pasteur, the mixture had two types of bacteria – Streptococcus pyogenes and Serratia mercescens inactivated, better known today for its role in nosocomial infections. He felt that this mixture, once injected, would encourage the body's immune system to attack and kill cancer cells.
Dr. Coley has injected this mixture with Zola several times until he develops a fever. Shortly after, Zola's tumor began to melt and eventually disappeared. This was perhaps the first case of cancer treated with modern day immunotherapy. Enthusiastic, Dr. Coley treated several other patients with sarcoma with Coley's fluid and, in 1893, published a report on this new mode of treatment in the American Journal of Medical Science. It was the first study on the use of immunotherapy to treat cancer.
Although very few people remember Zola's name and treatment, most people know Jimmy Carter, the former president of the United States. In August 2015, Carter announced that his melanoma was spreading to the brain and other organs. The situation seemed desperate, but his doctors took a radical approach: instead of the usual radiotherapy and chemotherapy practices, they decided to try immunotherapy, which saved Carter's life. The process used was developed by James P. Allison and Dr. Tasuku Honjo, this year's Nobel laureate of medicine for their groundbreaking work. Coincidentally, the duo will be awarded the prize on the occasion of the 125th anniversary of the first article, written by a New York bone doctor, on the use of immunotherapy to fight cancer .
The immunotherapy method of Allison and Honjo, however, is very different from that adopted by Dr. Coley. Current Nobel laureates have discovered a way to release the power of immune cells, particularly T cells, a type of white blood cell. In 1990, while working on T lymphocytes with Jeff Bluestone at the University of California at Berkeley, Allison discovered a protein – CTLA-4 – in T cells. Allison predicted that this protein would extinguish T cells, reason for which they do not attack the cancer cells. After another six years of research, Allison discovered how to block CTLA-4. This was the crucial moment in the immunotherapy of tumors. If CTLA-4 is blocked, T cells become active and can attack and kill cancer cells. Meanwhile, Dr. Tasuku Honjo from Kyoto University in Japan was also working on the same topic. He discovered an inducible gene, PD-1, which also prevented T cells from destroying cancer cells.
The discoveries of Allison and Honjo resulted in the development of checkpoint inhibitors, the first class of drugs designed to capture T cells in the fight against cancer. The US Food and Drug Administration (FDA) approved the first checkpoint inhibitor in 2011. The success of these drugs has been proven by the fact that their inventors received a Nobel Prize only seven years later.
Unfortunately, Dr. Coley's fate was very different. Although his magic soup, Coley's liquid, is used to successfully treat more than a thousand patients, his contemporaries regarded his success with suspicion because he could not explain why or how his treatment worked. In 1899, Coley's liquid became commercially available and in 1902, Coley received financial assistance from the Rockefeller and Huntington families – who would be the first private client to study cancer in the United States. Despite this, Coley's method was eventually replaced by radiation therapy. Perhaps the main reason is that Dr. James Ewing, who advocates radiation therapy and happens to be Coley's boss, called immunotherapy "dangerous." Dr. Ewing was the most famous pathologist of his time in the United States and, thanks to his plea, radiotherapy was officially adopted as a means of treating cancer.
Although we never know if Dr. Ewing discredited Dr. Coley's treatment because of professional jealousy, it is undeniable that the late nineteenth and early twentieth centuries were the era of radiation physics. The German physicist Wilhelm Roentgen, inventor of X-ray, won the first Nobel Prize in physics in 1901, while Pierre and Marie Curie won it in 1903 for their work on radiation. It was the taste of the time and scientists and their customers were more interested in radiation therapy. It was only after the scientific community understood the dangers of radio and chemotherapy that she began to be interested in immunotherapy.
While the efforts of Allison and Honjo to treat cancer with immunotherapy are truly pioneering, it is also true that it is time for immunotherapy. Dr. Coley was well before his time. Otherwise, Zola would be as famous as Carter, at least in the medical world.
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