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Therapeutic cancer vaccines are designed to stimulate the activity of the immune system against cancer cells. Natural anti-tumor immune response is often not efficient. Furthermore, specific targeting and activation of antigen-presenting cells (APCs) by a vaccine is challenging. Activated APCs (e.g. dendritic cells, macrophages) present antigens to T-cells which recognize and kill tumor cells. Currently, the only therapeutic oncologic vaccine approved by the FDA is Sipuleucel-T against prostate cancer. However, it requires isolation of the patient's dendritic cells, their stimulation in vitro and re-administration to the patient. Other methods of dendritic cells activation use antigen-containing nanoparticles tagged with antibodies having specific affinity for APCs.
In the latest issue of "Nature" magazine group of Prof. Ugur Sahin published their promising results on therapeutic cancer vaccines. The researchers from German Johannes Gutenberg University in Mainz have developed a new, simple method for activating dendritic cells without isolating them from an organism or tagging the nanoparticles with antibodies. They have used liposomes containing RNA encoding a tumor antigen. Due to a slightly negative charge, after intravenous administration, the liposomes have a high and specific affinity to the spleen and other lymphoid organs, where APCs reside. Studies of the vaccine efficacy were performed on several mouse models of lung cancer. Administration of the vaccine led to prolonged activation of specific T-cell response against tumor antigens and to regression of tumors. Furthermore, these vaccines have passed successfully pharmacological safety studies in mice and macaques.
Interestingly, the publication contains also preliminary results for three patients with severe malignant melanoma taking part in the phase I clinical trial (NCT02410733). The trial was designed to determine a safe dose of the vaccine. RNA used in the vaccines encode known, previously published melanoma-specific antigens. The doses applied were lower than in animal studies and did not cause serious side effects. After being given the vaccine, patients developed specific T-cell response. In the first patient, regression of suspected metastasis in a lymph node was observed. The second patient, whose metastases were removed surgically before vaccination, was tumor-free seven months after the immunization. Condition of the third patient, with eight metastases in the lungs was stable after vaccination.
The results are very promising, but it needs to keep in mind that one of the most difficult stages of the vaccine design is the selection of appropriate and specific cancer antigens. In this case, authors used known melanoma antigens. However, those antigens may not be expressed in all cases of melanoma nor in other types of cancers. Therefore, Prof. Sahin suggests, that in the near future tissue samples from each patient will be sequence to find individualized cancer antigens which will then be used for the vaccine production. He is co-founder of BioNTech AG start-up aiming to commercialize this technology.Source: www.nature.comSupporting material: Movie BioNTech AGImage credits: piyaphantawongImage source: FreeDigitalPhotos.net