03 June 2016

Step to victory over cancer: details

Universal anti-cancer vaccine helped the first patients

Oleg Lischuk, N+1

German scientists have developed a method for obtaining a universal anti-cancer vaccine. In early clinical trials, she successfully stopped the growth of tumors in three patients with melanoma. The results of the study are published in Nature.

Employees of the Johannes Gutenberg University with colleagues from other research centers have created a vaccine that contains RNA encoding tumor antigens. To prevent nucleic acid from being destroyed by extracellular ribonucleases, it was placed in lipoplexes (lipid nanoparticles). Tests of RNA-lipoplex complexes with various properties have shown that for their stable delivery to target cells, it is sufficient to adjust the total electric charge of the nanoparticle without functionalization by additional molecules.

RNA-lipoplexes.jpg
Lipoplex device diagram: nucleic acid (blue)
stabilized by two-layer lipid membranes

Experiments on mice have shown that after intravenous administration, RNA lipoplexes are effectively absorbed by dendritic cells (cells of the immune system that analyze antigens entering the body and inform T-lymphocytes about them, providing a specific immune response) and macrophages. In response, these cells secrete interferon-alpha and activate cytotoxic T-lymphocytes and memory T-lymphocytes. In an experiment with cancer antigens and tumors implanted under the skin, the vaccine completely prevented mice from developing cancer, while all unvaccinated animals died within 30 days.

After confirming the efficacy and safety of the vaccine in mice and crab-eating macaques, the researchers moved on to the first phase of clinical trials, in which the safety of increasing doses of the drug is checked. Scientists administered a vaccine containing tumor antigen RNA (NY-ESO-1, MAGE-A3, tyrosinases and TPTE) to three patients with metastatic melanoma. Therapy was started with a minimum dosage, after which several large, but not maximum doses were administered four times at weekly intervals. The trials have not yet been completed, but preliminary results confirm the effectiveness of the drug even in low doses.

In particular, the first patient had a decrease in the volume of metastases in the thoracic lymph nodes. The second participant had metastases surgically removed before vaccination, and no tumor recurrence occurred within seven months of follow-up. The third patient stopped the growth of eight metastatic tumors in the lungs.

The researchers note that it is possible to produce vaccines from RNA lipoplexes quickly and inexpensively, while they can contain almost any tumor antigens, providing universal immunotherapy for cancer.

Earlier in 2016, American researchers reported successful therapy of leukemia resistant to other treatments using genetically modified lymphocytes with chimeric antigen receptors. The majority of patients had a complete cure.

Portal "Eternal youth" http://vechnayamolodost.ru  03.06.2016

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