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The first time, it did not look so bad. Joaquin Fernandes' right leg had a small bulb, and like everyone else, he rejected it like a corn, something that would disappear from itself. Over the next few days, though, Fernandes noticed that the light bulb had started to turn black and decided to consult a doctor.
Doctors in his city – the Goa-born civil engineer has been working with a construction company in Dubai for three years. decades now-advised biopsy. "The results showed signs of cancer, doctors told me to go to India for treatment," he recalls
C was in 2015, and predictably, the news of melanoma was a big shock. " When it comes to cancer, we do not know anything. What to do, where to go … what will happen next? Fernandes said on the phone from Dubai.
But he thought that he had no time to lose and headed straight for Mumbai, a city where he has family. and a house too. At first, Fernandes, 60, consulted a doctor in a hospital in Mumbai and was told that the cancer cells would be removed by surgery. This would prevent the spread of cancer.
After the procedure, Fernandes felt better and returned to Dubai. But, true to its confused ways, cancer has fought back.
A few months later, Fernandes had pain in the groin. He returned to Mumbai, and this time the news hit him harder. "The scans revealed that the cancer had spread to the rest of the body," he says. And the hospital doctor in Mumbai had an even more shocking prescription for him. "He told me that they were going to cut off my entire body and remove the cancer cells manually." I was shocked to imagine myself in this state, to allow myself to "get out of bed." to be in a slaughterhouse. "
Fernandes had done her own research on the internet and had read about immunotherapy – the buzzword in the treatment of cancer. "People think that if you have cancer, it's the end.This is not so I've asked the doctor about immunotherapy." said that it was not possible in India, he said.
Not one to give up hope, Fernandes asked – many even told him about the quacks who made such procedures – and was referred to the famous Tata Memorial Hospital, where Fernandes met with Dr. Jyoti Bajpai, a medical oncologist, who told him that treatment was possible. "He had recurrent metastatic melanoma, which means that cancer can 39; was now spread in the body, and was in an advanced stage, "says Bajpai." Before the arrival of immunotherapy, melanoma was a kind of death sentence. The patients would not survive long. "
Like many oncologists around the world, Bajpai is also enthusiastic about immunotherapy, the principle on which it works is simple: in an ideal world, our immune system would fight cancer cells, just as it recognizes. other "alien" invading cells and kills them
. However, in cancer, something else happens … Round the cancer cells, even weaken the army of soldiers of the immune system, especially T cells, and continue their rampage Immunotherapy strengthens this army by several means and allows it to kill cancer cells.
The immune system recognizes foreign cells via "points of control "-molecules on certain immune cells activated (or inactivated) to trigger an immune response. [19659002ThesecontrolpointsisaproteincalledPD1(deathprogrammée)surleslymphocytesTSelonl'AmericanCancerSocietyPD1agitcommeun"switch"quiempêchelescellulesTd'attaquerd'autrescellulesIllefaitens'attachantàPD-L1uneprotéinesurcertainescellulesnormalesetcancéreusesQuandPD-1selieàPD-L1ilditauxcellulesTdelaisserlesautrescellulesseules
Some cancer cells contain large amounts of PD-L1, which helps them escape to an immune attack. Monoclonal antibodies targeting PD 1 or PD-L1, or CLTA-4 (a protein receptor), can block this binding and let immune cells attack cancer cells
. For Fernandes, the answer lies in two drugs: ipilimumab. , which was the first to extend the survival of patients with advanced melanoma, and nivolumab (sold as Opdivo). These "checkpoint inhibitors" have been found to be extremely effective for advanced melanoma.
For about six months, Fernandes went to Mumbai every three weeks and injected it. "His scans began to show positive results after a few doses," says Bajpai, a professor at Tata Memorial Hospital. "Now he is in remission, we are going to monitor him for several years.The first two years are critical because it is at that time that the disease could reappear."
Immunotherapy, says it has been approved for nine types of cancer now, it has been found to be effective in melanoma, in lung, bladder, head and neck cancers, its role has been defined, in sarcomas , ovaries and bad cancer, it is still in the early stages of the trials
Several oncologists who we spoke to described this mechanism as "exciting," "revolutionary" and even as a "paradigm shift" in the cancer treatment and also, at an advanced stage, where conventional therapies have failed.
"When it comes to more aggressive cancers, at an advanced stage, and in solid tumors such as lung cancer, esophageal cancer, liver and brain, we have reached a plateau in cancer treatments, "says Dr. Rakesh Jalali, medical director of the Apollon Proton Cancer Center in Chennai. "In the last five to ten years, however, immunotherapy has ushered in a new revolution."
For those who have no option, for whom all conventional treatments have failed, immunotherapy is a "revolutionary" treatment.
The idea itself, says Jalali, is not really new. For centuries, it has been known that a strong immune system can fight cancer, and scientists have been trying to exploit the immune system to do it.
Recently, they have had some success, particularly with the checkpoint inhibitors that have been approved 2011 and, more recently, with the T cell therapy of the chimeric antigen receptor (CAR) . Last year, the US Food and Drug Administration approved two CAR T cell therapies, one for the treatment of children with acute lymphoblastic leukemia, and others for adults with advanced lymphoma . The therapy, used in blood cancers, requires extracting the blood from the patients and separating the T cells. Then, using a disarmed virus, the T cells are genetically engineered to produce receptors on their surface called receptors of chimeric antigens. These receptors allow T cells to recognize and bind to a specific protein, or antigen, on the tumor cells. Once remodeled, these cells are multiplied in the laboratory and planted in the patient's body, where they multiply and destroy the cancer cells by recognizing them by their receptors.
In India, checkpoint inhibitor therapy has made its way years, and research on CAR T cell therapy is still in its infancy. "Unlike chemotherapy, where we attack cancer cells with drugs and work on the maximum limit of body tolerance, in immunotherapy, we simply strengthen the immune system against cancer," says Dr. Gaurav Narula, professor of pediatric oncology and facilitator, Pediatric Hemato-Lymphocytic Group at the Tata Memorial Center, Mumbai, who worked on T-cell CAR therapy in India, with his partner at IIT Bombay. Overall, the therapy has found some success in about 15% of blood cancers that do not respond to chemotherapy.
The advantage of immunotherapy against conventional treatments lies in its reduced toxicity, says Dr. Vinod Raina, department head and director of Medical Oncology and Hematology, Fortis Memorial Research Institute, Gurugram. "The side effects are not the clbadic effects such as hair loss and a drop in white blood cells.However, some immunotherapy drugs may show side effects such as colitis and hepatitis," says
For Fernandes, however, things went rather smoothly.He, of course, experienced some fatigue, and some rashes, but not the most serious side effects. " was really lucky, because the drugs have cured my diabetes and even myopia, "he says
.The cost, however, is a big challenge in immunotherapy." There are no generic drugs, so these drugs used in treatment are expensive, "says Raina." In lung cancer, the cost is a bit less, because the Indian government controls the price. In fact, it's cheaper than in the United States. But not for those used in other cancers. "The cost of treating lung cancer would be up to Rs 1 lakh every 15 days," he says, and the treatment could last up to six months.
In India, says Raina, the cost factor becomes even more important because head and neck cancers are common among the poor, for whom this therapy is out of bounds.
Fernandes, the cost was even higher because, in 2015, the drugs were imported from the United States. "The treatment cost me 50 Rs lakh," he says. "Add another Rs 50 lakh for hospital stay, tests, trips and other personal expenses . I've been lucky that my company covers all my costs. "
Bajpai says that more trials in India could help because, in Indian patients, shorter doses are working, and costs can therefore be reduced.In addition to the cost, oncologists warn that hype around Immunotherapy might not be worth it. "It's a mixed bag. All of the checkpoint inhibitor drugs do not work, and some medications are actually quite useless, "says Raina.
For all the buzz around him, only 40 percent of patients will respond to this treatment, says Jalali. "It's not a magic wand," he says. Complications can wreak havoc in the system, and you also need a different criterion, instead of standard badysis, to judge if the cancer is gone, he says.
"This is certainly not a panacea for all types of cancers." Narula said. In practice, immunotherapy, particularly CAR T cell therapy, could pose several problems. "It's after all a living drug in your body, and sometimes it could also attack normal cells," Narula says. The remodeled T cells may release a large amount of cytokines (chemical messengers that help stimulate and direct the immune response), triggering a high fever and a drop in blood pressure. In addition, they could also attack B cells that produce antibodies. But these two side effects are managed.
"Still, it's not easy – once you've removed the T cells and remodeled them, you also need to keep the patient alive for two to three weeks when the cells are worked. in the lab, "says Narula.
The opportunity in immunotherapy is immense, says Jalali." We need to collaborate with the global community and be intellectually honest about test results, "he says.
Although doctors monitor Fernandes every three months, the way his body responded offers hope to several cancer patients. "Cancer is not the end, people need to know it. However, one must have the courage to try something new, "explains Fernandes.
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