Melanoma vaccines
Two personalized melanoma vaccines have been successfully tested on humans
Two research groups from different countries conducted clinical studies of individual melanoma vaccines, which confirmed their effectiveness and safety.
Melanoma is a tumor of a high degree of malignancy, in which pigmented skin cells under the influence of various factors degenerate into malignant. One of these factors is genetic mutations that disrupt the processes of cell division, causing their abnormal growth, or prevent their natural self–destruction. Most often, 4-6 different genetic mutations are required for the occurrence of melanoma, but there are such genes in which only one is enough.
Melanoma is difficult to treat with traditional treatment, but it is susceptible to immunotherapy – the introduction of monoclonal antibodies to cancer cells into the patient's body. The next step in the treatment of melanoma is the introduction of personal vaccines that will create the patient's immunity specifically to his tumor.
A team of scientists from the Dana-Farber Cancer Research Institute, Brigham Women's Hospital and Harvard Medical School (USA) conducted a clinical study of a personalized vaccine against tumor antigen. The vaccine was developed individually for each study participant. Scientists sequenced the tumor genome of each patient, identified a set of mutations peculiar only to her and created a vaccine directed against the cells of this particular tumor.
A complex of mutations peculiar only to this tumor is called a mutan. Mutan causes tumor cells to produce proteins that are foreign to the body. These proteins are not present in healthy tissues, so their presence in the vaccine causes a high immune response. The recipient's body produces T-lymphocytes that attack tumor cells containing these antigen proteins. This helps to destroy the cells of the primary tumor and prevent metastasis and relapses.
Six patients participated in the study. After vaccination, four subjects had no relapses for 25 months. In two patients with recurrent tumor who also received immunological treatment after vaccination, complete regression of the tumor and an increase in the number of tumor-specific T-lymphocytes were observed.
An Austrian-German group of scientists applied individual neo-epitope vaccines to patients with stage III and IV melanoma. Scientists have identified mutanomas individual for each patient's tumor and developed vaccines specific to the epitopes of each of them. (An epitope is a section of an antigen protein molecule that binds to antibodies.) In this study, 125 types of mutations were identified, while the vaccine that the Americans tested works against 20.
All patients underwent a course of 20 vaccinations, which they underwent without serious side effects. In response to the use of vaccines, all study participants developed T-lymphocytes that work against tumor cells. In general, the participants were immune to 60% of the 125 identified mutations, and each patient had T cells against at least three mutations. The total number of cases of metastasis in patients has significantly decreased, the survival time without disease progression has increased.
According to the authors, polyvalent neo-epitope vaccines can prevent the recurrence of melanoma in high-risk patients both in monotherapy and in combination with monoclonal antibody preparations.
Both studies have shown high efficacy and safety of individual melanoma vaccines based on the analysis of mutations of specific tumors of patients.
Both studies are published in the journal Nature: Ott et al., An immunogenic personal neoantigen vaccine for patients with melanoma; Sahin et al., Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
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06.07.2017