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Cancer of the patient's head and neck erupted backward, spreading to his lymph nodes and skin, resulting in bleeding. Yet despite a bleak prognosis, this man is alive and without cancer more than two years later.
In a study conducted by the University of Pennsylvania and published Friday, the researchers speculate that its remarkable remission is due to a promising combination: an experimental cancer vaccine that activates its anti-disease T cells and Opdivo, an inhibitor revolutionary. drugs that slow down the immune system.
"Of course, I am biased," said Charu Aggarwal, Penn's oncologist who led the study. "During my career, I have not seen a vaccine as important as that."
However, the remission may be due to Opdivo alone; the study lacks data to rule out this possibility.
Robert Ferris, head and neck surgeon at the University of Pittsburgh Medical Center, who led the landmark study leading to Opdivo's approval, described Penn's important mid-stage study as exploring a strategy that we hope will work.
Conventional vaccines prevent disease by priming the immune system to recognize the distinctive "antigens" of invading microbes. Therapeutic cancer vaccines, like the one in this study, are designed to act after cancer development by inducing an increased immune response.
Despite decades of research, this approach remains experimental. The only approved product, the Provenge Prostate Cancer Vaccine, was barely effective; The manufacturer filed for bankruptcy in 2015.
A major obstacle to vaccine treatment is the fact that the cancer comes from the cells of the body. Although cancer cells produce antigens as they mutate, the use of these revealing proteins as targets of the immune system has proven to be very difficult.
Despite this, at least four pharmaceutical groups are developing therapeutic vaccines targeting human papillomavirus, HPV, the sexually transmitted virus that causes cervical cancer, head and neck cancer, and certain cancers. rare genitals.
These diseases can be prevented with the recommended HPV vaccine for all adolescents, but it did not exist 12 years ago. To the dismay of the public health authorities, vaccination rates remain low. And while screening can detect and treat precancerous cervix, there is no method of early detection of head and neck cancers; experts call the growing incidence of these malignancies an "epidemic".
The vaccine in the new study, called MEDI0457, was originally developed by Inovio with pioneer technology at Penn. In 2015, MedImmune, part of AstraZeneca, acquired exclusive rights to the drug.
MEDI0457 contains a DNA ring called plasmid that programs the patient's cells to produce two HPV antigens. The vaccine is injected into the patient's muscle and enters the cells using a small electrical impulse applied to the skin. When the cells make the antigens, it triggers the immune system to activate white blood cells that fight the disease, called "killer" T cells.
For the study, published Friday in Clinical Cancer Research, 22 patients with head and neck cancer received conventional treatment – surgery or chemotherapy and radiotherapy – that eliminated all signs of cancer. This was supplemented with four doses of the experimental vaccine, which caused no serious side effects.
Eighteen patients, or 80%, had high T cell activity at least three months after the last dose of vaccine. While this is an encouraging sign, the study was too preliminary to detect clinical efficacy such as tumor shrinkage or improved survival.
In the recurrent patient, the cancer reappeared seven months after treatment and spread to the lymph nodes and skin. He received Opdivo and eight weeks later the cancer was gone.
Aggarwal and his co-authors note that such remarkable remissions sometimes occur with checkpoint inhibitors. But they assume that the vaccine accelerates the patient's T cells, and then Opdivo eliminates the immune brake, allowing T cells to attack the cancer.
"The response suggests that the vaccine could, in a way, boost the immune system, which could stimulate the effects of further treatment (checkpoint inhibitor)," said Aggarwal.
Rajarsi Mandal, director of head and neck cancer immunotherapy at Johns Hopkins University, has taken a more conservative stance. "They have very well demonstrated the reactivity of T cells. But there is not much data suggesting that the vaccine induces a clinical response in these patients. Overall, it's interesting, but not incredibly revolutionary.
Nevertheless, the combined approach is promising enough that MedImmune is currently funding a clinical trial conducted by Penn on MEDI0457 and MedImmune's experimental checkpoint inhibitor.
Ferris, meanwhile, said that it was part of a trial of a competing experimental vaccine for HPV-related cancers, as well as the approved checkpoint inhibitor, Keytruda.
"The HPV preventive vaccine works very well," he said. "But if you are too old to get it, you can boost the immune system so that it fights cancer. This (new study) suggests the next logical step. "
© 2018 The Philadelphia Inquirer
Copyright 2018 Tribune Content Agency.
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