2023-06-07 12:39:02
Cancer is a disease, in general, very unpleasant, due to being restrained in its classification, but there are cancers much more unpleasant and dangerous than others. One of the worst, without a doubt, is pancreatic cancer, in fact, the so-called adenocarcinoma of the pancreatic duct.
Adenocarcinomas are cancers that originate in the glandular cells of an organ. These cells are responsible for producing and secreting substances such as mucus, enzymes or hormones. Adenocarcinomas can develop in all organs of the body that have glandular cells, including the lungs, colon, pancreas, prostate, breast and uterus, among others.
As I said, pancreatic adenocarcinoma is one of the most dangerous tumors. This type of tumor is the third leading cause of cancer death in the United States and the seventh worldwide. Unfortunately, its incidence is increasing, but its survival rate is small, only twelve percent of patients, a rate that has remained practically unchanged over the last sixty years, and this despite the enormous advances made to treat and cure other types of cancer. And surgery remains the only curative treatment for pancreatic adenocarcinoma. However, even when surgery is successful, without additional treatment nearly ninety percent of patients suffer a recurrence of the disease in an average period of only seven to nine months. The overall five-year survival after being diagnosed is only eight to ten percent. Come on, being diagnosed with pancreatic cancer is, today, almost equivalent to a death sentence.
Fortunately, there are chemotherapy treatments capable of delaying the recurrence of this disease after surgery, which are now standard in hospitals. However, despite these treatments, almost eighty percent of patients suffer recurrent disease around fourteen months after surgery and less than thirty percent survive more than five years in these conditions. Radiotherapy, biological treatments and other types of therapies have also proven ineffective.
As if this were not enough, pancreatic adenocarcinoma also cannot be treated with the newest and most effective immunotherapy, which is called blocking point immunotherapy. Despite the name, the way this immunotherapy works is very easy to understand. Tumors are kept at bay under normal conditions thanks to the generation of killer T lymphocytes, which detect and eliminate them, killing the tumor cells. However, tumors can prevent the action of these killer T lymphocytes by producing substances that block them and prevent their action. This way the tumor can grow. Well, blocking point therapy is aimed at preventing the blockade that tumors carry out on the T lymphocytes. Once the blockade is prevented, the killer T lymphocytes can kill the tumor cells and the tumors, in many cases, can be eradicated.
As I have mentioned, this immune therapy is not effective in treating pancreatic adenocarcinoma. One reason that could explain this fact is that perhaps pancreatic tumors do not generate new antigens that can be detected by killer T cells. In general, tumors, throughout their progress, suffer mutations in several genes, which cause them to generate new antigens that make them foreign entities for the cells of the immune system. By detecting these foreign antigenic proteins, they are able to identify tumor cells as dangerous and eliminate them. Obviously, if a tumor does not generate new antigens, that is, it does not mutate enough to appear foreign to immune cells, they will not react against it. Under these conditions, blocking point immunotherapy will not be effective, since there will be no T lymphocytes that have been blocked by the tumor. On the contrary, these lymphocytes will not have even been generated to begin with.
Initially, it was thought that the reason why pancreatic adenocarcinomas did not generate T lymphocytes against them was this, that they did not produce new antigens against which these lymphocytes could react. However, recent studies have shown that this is not true. Pancreatic tumors mutate, and generate antigens, but for some reason, not enough killer T cells active against them are generated.
In this state of affairs, researchers at the Sloan Kettering Cancer Institute in New York had the idea of trying to use messenger RNA vaccine technology to stimulate immunity against pancreatic tumors. Perhaps, they said, by stimulating the immune system cells intensely with the same antigens produced by the pancreatic tumor, killer T lymphocytes would be generated to defend themselves against its progression.
The idea was excellent, but it ran into the problem that each tumor, in each patient, mutates differently. This means that the new antigens generated by the tumor, those that identify it as foreign, are not the same from patient to patient. It is, therefore, not possible to produce a generic vaccine against all pancreatic tumors. If we want the vaccine to be effective, it must be generated specifically for each patient. How can we do it? Is that possible?
Modern biomolecular technology makes it possible to acquire the letter sequence of the genes that are functioning in a tumor and compare it with the letter sequence of the genes of the normal cells of the same patient. This comparison allows us to identify which genes have mutated and which new antigens have been generated.
With this information, it is now possible to produce, for each patient, messenger RNA vaccines, similar to those we have all received during the COVID-19 pandemic, to stimulate the immune system of each patient with the new antigens that, due to mutations at the chance, has been generating its particular tumor. This stimulation should normally be more powerful than what the tumor cells provide to the immune system, so the immune system would be activated at higher levels and be more effective than normal in eradicating tumors.
Researchers are thus able to generate personalized messenger RNA vaccines for each patient. In a first trial, they study its effectiveness in sixteen patients with pancreatic adenocarcinoma and find that the vaccine is effective in eight of them. It’s a good start.
There remains, of course, much to study before we can achieve messenger RNA vaccines with higher efficacy. It is hoped, however, that this will be achieved before another sixty years pass without more effective therapies for pancreatic cancer than those currently available. It is also certain that what is learned with these vaccines will also help to generate messenger RNA vaccines against other types of tumors, which are easier to cure, but for which these vaccines would also be useful.
In conclusion, allow me to say that science does not always progress at the desired speed, but there is no doubt that, if we treat it with love, responsibility and sensibility, it will end up progressing and will more than return what we invested in it.
And that’s all for today. May you be happy, may the good antibodies accompany you, and may the good T lymphocytes do so on this occasion as well. Good science and until the next program. Bye bye.
Referencia: Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.
Works by Jorge Laborda.
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