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The idea of causing the immune system to hunt cancer cells and kill them has been confirmed by two FDA-approved CAR-T treatments for lymphoma, Novartis' Kymriah and Gilead's Yescarta, which both involve the removal of T cells from patients and their engineering. to be able to recognize cancer. But what would happen if an effective immune attack against lymphoma could be achieved by injecting drugs directly into the tumors?
Researchers at the Mount Sinai School of Medicine in New York have promising evidence that this approach, called "in situ vaccination," could be effective in the fight against lymphoma. Their results were so encouraging that they opened a clinical trial not only on lymphoma but also on breast cancer and head and neck cancer, Mount Sinai said in a statement.
The vaccine consists of two drugs administered to the tumor sites. According to the statement, the compounds work together to help the T cells of the immune system kill cancer cells throughout the body.
In murine models, the vaccine produced remissions in 40% of animals. When the treatment was associated with drugs that block the PD-1 immune "checkpoint", 80% of the mice had sustained remissions.
Mount Sinai researchers then tested the vaccine in 11 patients with advanced non-Hodgkin's lymphoma. Eight patients presented partial or complete responses in the treated tumor sites and three were in remission. The results were published in the journal Nature Medicine.
RELATED: Anti-tumor "vaccine" eliminates several types of cancer in mice
The Mount Sinai approach relies on a process that they call "crossover priming". First, they recruited dendritic cells into the immune system using the Fms type tyrosine kinase ligand 3 (Flt3L). Then they activated the dendritic cells using radiation and a drug called TLR3 agonist. Once activated, dendritic cells explain to T cells how to look for and destroy tumor cells throughout the body.
"We expected direct priming to explain the rapid clearance … of the tumor, but we were surprised to see that clearance of the tumor was entirely dependent on crossover priming," the authors wrote. of the study.
Celldex Therapeutics, developer of immuno-oncological drugs, and Merck, which manufactures Keytruda, the PD-1 inhibitor, are among the organizations that have supported research. Celldex, which is currently regrouping following several disappointments in its pipeline, provided Flt3L for the study.
The injection of immunostimulatory agents directly into the tumors is an idea that several researchers are pursuing, looking for ways to improve the efficacy of immuno-oncological treatments. Last year, Stanford University opened a clinical trial of an anti-tumor vaccine combining a short segment of DNA and an antibody that binds to the OX40 protein, stimulating T cells to eradicate cancer cells.
The start-up Elicio Therapeutics recently raised $ 30 million to continue its approach of administering cancer vaccines via the lymph nodes. Gileadeaded Hookipa Pharma is seeking more than US $ 86 million as part of an initial public offering to develop its platform, which uses viruses to boost the immune response of dendritic cells.
Although Mount Sinai's initial small trial of the in situ human vaccine was not designed to test a combination of the vaccine with MP-blocking drugs, the results in mice strongly suggest that this could improve the efficacy of the vaccine. effectiveness of checkpoint inhibitors, wrote the authors. The newly opened clinical trial will test a combination of the vaccine with Keytruda, Mount Sinai said.
"We demonstrate here that increasing and enabling cross-presentations [dendritic cells] on the site of the tumor can initiate a specific tumor [T cells], restore the effectiveness of blocking control points and give superior anti-tumor immunity, "wrote the authors.
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