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In carcinomas, cancer cells often gain the loyalty of neighboring cells, stromal cells, which one should better know. Rather than staying out of the way and letting the immune system eliminate the cancer cells, gullible stromal cells, or connective tissue cells, interfere. They protect the cancer from the immune system and provide it with growth factors and nutrients. Although cancer cells are prone to a robust immune response, duped stromal cells can ensure that enough cancer cells survive to stage the resurgence of cancer.
One way around this difficulty in treating cancer may seem obvious or even ruthless: kill cancer cells and the duped cells. But there is a problem: it is difficult to kill stripped cells without also killing wiser and more sensitive stromal cells throughout the body. Scientists from Oxford University, however, suggested a potential solution.
According to these scientists, led by oncologist Kerry D. Fisher of Oxford, Ph.D., a vaccine already used in clinical trials as an anticancer treatment can be modified so that cancer cells betray their protectors. That is, the cancer cells are made to take their friendly stromal cells with them.
The nearby cancer cells and fibroblasts are killed (bright green flashes) by the Enadenotucirev virus equipped with a bispecific T-lymphocyte developer. The cancer cells (unstained: black) are infected with the virus and actively secrete the virus. 39, bispecific inspector of T lymphocytes before dying. The T cell injector forces T cells (small, round and blue) to attach to (red) fibroblasts and kill them. [J Freedman/Cancer Research]
How? The vaccine, an oncolytic virus called Enadenotucirev, causes cancer cells to produce a protein called bispecific T cell transplant (BTE). BiTE is designed to bind to two types of cells and stick them together. In this case, one end is targeted to bind to the fibroblasts. The other end specifically adheres to T cells, a type of immune cell responsible for destroying defective cells. This triggers T cell destruction of the attached fibroblasts.
The details of this new approach to immunotherapy were published in the journal Nov. 18. Research against cancer, in an article entitled "An oncolytic virus expressing a T cell mobilizer simultaneously targeting cancer and immunosuppressive stromal cells". anti-fibroblasts (CAF), but also to CD3ε on T cells, resulting in potent T-cell activation and fibroblast death.
"Treatment of fresh clinical biopsies, including malignant ascites and solid tissue of prostate cancer, with virus-induced activation of FAP-BTE, of infiltrating PD1 in the tumor+ T cells to kill the FAC, "said the article's authors. "In ascites, this resulted in a decrease in CAF-associated immunosuppressive factors, a positive regulation of proinflammatory cytokines, and increased gene expression of markers of antigen presentation, T-cell function, and trafficking. M2-type ascites macrophages exhibited pro-inflammatory repolarization, indicating alteration of the tumor microenvironment at the spectrum level. "
"We have diverted the machinery from the virus so that the T-cell injector is made only in infected cancer cells and nowhere else in the body," said Joshua D. Freedman, Ph.D. author of the study. "The T cell commitment molecule is so powerful that it can activate the immune cells inside the tumor, which are suppressed by cancer, to attack the fibroblasts."
"Our new technique to simultaneously target fibroblasts while removing cancer cells with the virus could be an important step in reducing the suppression of the immune system in carcinomas and should revive the normal immune process," said Dr. Fisher. . "These viruses are already being tested on people, so we hope that our modified virus will head to clinical trials as early as next year to determine whether it is safe and effective. in people with cancer. "
Scientists have successfully tested the therapy on human cancer samples taken from consenting patients, including solid tumors of prostate cancer that reflect the complex composition of actual tumors. They also tested the virus on healthy human bone marrow samples and found that it did not cause toxicity or inappropriate activation of T lymphocytes.
The virus targets carcinomas, which are the most common type of cancer that start in skin cells or in the tissues that line or cover the internal organs, such as the pancreas, colon, lungs, breasts, the ovaries and the prostate.
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