More than a century ago, New York surgeon William Coley observed that tumors with some infection tended to subside. Bacteria or viruses in the area where cells were multiplying uncontrollably alerted the immune system, which until then had not realized the anomaly that was occurring. Scientists believe that it is very possible for our defenses to slow down many tumors before they are detectable; what we know as cancer would be those cases in which the malignant cells have deceived our immune system and have managed to spread hidden from it by several mechanisms.
Coley experimented with this idea by inoculating streptococci to the tumors to alert the body’s defenses. He did it with some success, but above all with failures, since the toxicity of the bacteria caused more problems than solutions. Cancer research took other courses. Terribly aggressive treatments were discovered, but more effective, such as chemotherapy, which intoxicates the cells to kill them, or radiotherapy, which does something similar, but in a more focused way.
The side effects and the lack of a definitive solution against cancer caused that the idea of stimulating the immune system, which always went dormant, would regain strength a few years ago. The advances made in basic research earned immunotherapy the recognition of scientific discovery of 2013 , according to the prestigious journal Science . Since then, the field has only made progress. Only 1% of the studies presented at the congress of the American Society of Clinical Oncology (ASCO) were based on this technique three editions ago; the figure went up to 10% in the next and a quarter of the papers were talking about immunotherapy at the last congress.
This exponential growth gives clues to where cancer research is going. Two disciplines that practically turned their backs on for years (oncology and immunology) now go hand in hand to the point that these oncological treatments have been one of the star themes at the International Immunology Congress that was held last week. in Melbourne.
Although for many types of cancer immunological treatments are still very experimental, this technique is a relatively established reality for others. A living example is Susanne Harris, who nine years ago suffered a strange melanoma that refused to disappear with conventional therapies. In 2013 he enrolled in what was then an essay. She had to go every three weeks from Melbourne, where she lives with her husband, to Sidney, so that for half an hour they would inject a drug called Keytruda. In less than two months the tumor was already remitting. After 12 almost could not be seen. In November it will be a year ago that he stopped receiving treatment and the tumor has disappeared, as the last scanner showed a couple of weeks ago, which came to endorse all the previous ones. “All without the slightest side effect”,
His isolated case could be anecdotal or the result of chance, but it is one of the hundreds that swell the evidence of the effectiveness of this treatment. Although the evidence that it can work is robust, so are its tremendous selectivity. It only works in about 24% of patients. Jonathan Cebon, director of the Cancer Research Institute Olivia Newton-John, who has participated in the experiment that saved Harris’ life, recognizes that one of the great challenges is to know why in the same tumors immunotherapy works only in a few subjects.
In the case of melanoma, however, it is especially encouraging. It has benefited from the little success that chemo and radiotherapy have against this type of cancer. Half a dozen treatments have already been approved by the American FDA. Cebon says that by combining them the effectiveness reaches 80%. “But they are figures that are in constant movement depending on the advances that are presented,” he says.
Although all treatments with immunotherapy are based on helping the body’s own defenses to locate and eradicate cancer, there are several mechanisms of action. In the case of Keytruda, it is based on neutralizing a protein on the surface of cancer cells known as PD1, which prevents lymphocytes from fighting against them. Much of the oncological research is to neutralize them so that the body can kill the tumors.
Other techniques involve removing white blood cells from the patient, either from the tumor itself or from outside the tumor, selecting those that have greater antitumor activity to grow and activate them and, finally, implant them again in the patient. It is a somewhat more experimental method than the previous one; Scientists are investigating how to manipulate these cells to make them more effective against tumors.
Vaccines are a third way of immunotherapy against cancer. But not preventive, such as those used to stop measles or flu, but therapeutic, when the patient already has the disease or even when it has overcome. The goal is to warn the immune system, which for some reason has not noticed the existence of cancer, that is there. This is usually to extract cancer cells that are manipulated so that the defenses can give a correct response to the tumor. The first vaccine of this type was approved in the United States in 2010 and is used for some types of prostate cancer that have spread.
But as cancer is not a single disease, but an umbrella that encompasses many processes, it is difficult to find a single vaccine that can stop or treat the progress of all types of tumors. Each one requires specific research, which takes into consideration how cells propagate, their characteristics, their stage …
Vaccines can work by stopping the proliferation of cancer cells, reducing the tumor, eliminating those that have not been eradicated with other treatments or preventing it from reappearing. The latter is trying to achieve this with prostate cancer Jay A. Berzofsky, director of the immunogenetics and vaccines section of the National Cancer Institute of the United States . The results of the first phases of his research, which he presented at the International Congress of Immunology in Melbourne, have shown a positive evolution in 75% of patients. It is, however, a very premature stage, in which the effectiveness has not yet been compared with a control group that is under a placebo treatment.
The advantage that prostate cancer has to investigate vaccines in it is that there is a biological marker that indicates its evolution, the PSA. What Berzofsky’s team has done is to inoculate the vaccine after removing the tumor and observing the levels of this substance. In three quarters of the patients the levels reduced their growth after the administration of the immunization, which gives clues to their possible effectiveness. “If successful, this same vaccine could also be effective against a type of breast cancer, what happens is that it is more difficult to experiment with it,” says the researcher.
But the truth is that the road that lies ahead is long. In the most optimistic scenario, Cebon calculates that in 10 years immunotherapy can replace the most aggressive treatments in several types of cancers such as prostate, melanoma, stomach and breast. But the opinion of the majority of the scientific community is that even in those for which it is effective, it will often have to be combined with surgery, radio and chemotherapy, says Robert G. Ramsay of the Peter MacCallum Cancer Institute in Melbourne.
The other big question about immunotherapy that needs to be answered is whether it definitely cures the cancer or just treats it. The drugs are so new that patients who have benefited from them are still being observed to see if the tumors reappear. Laurie H. Glimcher, president of the Dana-Farber Cancer Institute in Boston, is reasonably optimistic: “We hope these treatments prevent our children and our grandchildren from dying of cancer. In the future it will be a chronic disease, and not a fatal one, as happened with HIV. “