A clinical suggestion, on which however it is worth working. Having not so far obtained the results hoped for by immunotherapy, researchers committed to finding new effective solutions against pancreatic cancer have gathered an encouraging result. The protagonist is an evolution of gene therapy, which in oncology is defined with an acronym: Car-T. In a woman with lung metastatic disease, using laboratory-engineered T lymphocytes to recognize cancer cells resulted in a significant (-72 percent) reduction in formations in both respiratory organs. A result recorded months after the infusion, a considerable time since it is the form of cancer burdened with the highest rate of lethality.
Pancreatic cancer: early diagnosis in the future with a stool test
by Mara Magistroni
A story that bodes well
The protagonist of this scientific success – reported in an article published in the New England Journal of Medicine – is a 71-year-old woman from Florida: Kathy Wilkes. In 2018, following investigations conducted to clarify the origin of several episodes of pancreatitis and biliary stenosis, the patient was diagnosed with adenocarcinoma of the head of the pancreas. Like about 20 percent of people who discover they have this disease, Wilkes underwent chemotherapy, surgery, chemo, and radiation after the operation. A tiring journey, which, however, was not enough to avoid the appearance of lung metastases. In front of her, two paths: a new cycle of chemotherapy or the inclusion in a research protocol that involved the use of engineered T lymphocytes to “arm” the immune system against the disease. A road already traveled in 2016 in a patient with metastatic colon, who shared with Wilkes a salient trait of the disease: the mutation of the KRAS gene, the most common in tumors of the gastrointestinal tract. This variation in DNA, present in approximately 45 percent of pancreatic cancer diagnoses, is referred to as the “driver”. That is, capable of guiding cell proliferation from a tumor perspective. Hence the idea of US researchers – Provider Cancer Institute of Portland and National Cancer Institute of Bethesda – to involve women in this trial.
Another person’s T lymphocytes “trained” to fight pancreatic cancer
In June of last year, the patient undertook the new procedure. The infused cells were T lymphocytes from a donor and engineered in the laboratory to allow them to recognize cancer cells and direct the immune response against them. Or rather: precisely against the mutation of the KRAS gene. An approach that follows that of the Car-T already authorized for the treatment of some haematological and lymphatic system cancers. But more complex in preparation. In fact, before the infusion, the woman underwent a course of chemotherapy (to reduce the risk of the patient’s immune system rejecting the donor’s T lymphocytes) and the administration of tocilizumab (another immunosuppressant). Five days later she began treatment with interleukin-2 in order to stimulate the immune response. The result – favored by the rapid production of cytokines such as interferon gamma, tumor necrosis factor and interleukin-2 – was encouraging. It is free from side effects. “The seven lung lesions had already regressed during the first visit, carried out 40 days after the infusion”, is what the researchers, coordinated by the oncologist Rom Leidner, put in black and white. A new metastasis was found nine months later. “She was removed and the patient was disease free for up to four months after surgery.” A significant finding, considering the often poor prognosis that accompanies pancreatic cancer, when it has already spread remotely.
Another patient who was treated in the same way died
Although in another case treated in the same way the experimentation gave a negative result, the result reported in the article bodes well. In an editorial also published in the New England Journal of Medicine, Cornelis Melief explained the mechanism behind the observed response. “The immune system, through some receptors, is able to recognize the mutations that guide the evolution of an oncological disease – as illustrated by the director of the department of immunohematology and transfusion medicine of the University of Leiden (Holland) -. the reinfused T cells were modified to recognize one of the mutated peptides in the KRAS gene. The good news is that all patients expressing this KRAS mutation could potentially benefit from this therapy. ”
The need to support the immune system
The approach – it should be pointed out – remains experimental. And, according to the available data, not suitable for all patients. “Having considered a single case, with metastases limited only to the lungs, does not allow us to unbalance the clinical impact of the treatment – says Michele Milella, director of the medical oncology department of the integrated university hospital of Verona -. The underlying concept is very interesting. Up to now, in fact, immunotherapy has not given great results against pancreatic cancer. These results have two possible explanations: the blockage put in place by cancer cells against the immune system and the scarce production by the same cells of recognizable and attackable antigens. The infusion of healthy T lymphocytes represents an aid from the outside, which aims to force the action of the patient’s immune system. The first response was positive. It will be necessary to verify the outcome of the same treatment on a larger number of patients. As well as, of course, its duration over time “.