Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs. We isolated dendritic cells from peripheral blood monocytes and delivered our constructs to these cells by magnetic transfection. Additionally, a series of experiments with loading of dendritic cells with autologous tumor cell lysate antigens was conducted. We have shown that dendritic cells transfected with the HLA-A*02:01-restricted DNA constructs are effective in inducing an antitumor response in a culture of mononuclear cells of breast cancer patients. Dendritic cells transfected with DNA constructor dendritic cells loaded with lysate antigens revealed a comparable stimulated cytotoxic response of mononuclear cells to these two ways of antigen delivery. We conclude that using DNA constructs in conjunction with patient stratification by HLA type allows the application of transfected DCs as an effective method to stimulate antitumor immunity in vitro.
Breast cancer is the most common oncological pathology in women worldwide. Techniques for improving the clinical parameters of patients undergoing combination therapy for breast cancer are currently under development. A type of treatment employing dendritic cells (DCs) and cytotoxic DC-induced antigen-specific T lymphocytes efficiently eliminates residual cancer cells that are the key cause of tumor recurrence and metastasis. In the present study, DCs and activated lymphocytes (treated with IL-12 and IL-18) were isolated from the peripheral blood of patients with breast cancer, using a lysate of tumor tissue as antigen. The patients received the cells as part of adjuvant or neoadjuvant regimens (stage IV disease or progression). Evaluation of immunity was performed at 3 and 6 months after terminating immunotherapy. Evaluation of the disease-free period was performed for 3 years after surgery. The use of antigen-loaded autologous DCs combined with mononuclear cells with increased cytotoxic activity following Th1 polarization reduced the populations of immunosuppressive cells. The results of the present study demonstrated that the investigated cellular immunotherapy for breast cancer is safe, reduces the risk of relapse and metastasis, and improves immunity by reducing the number of regulatory T cells. Therefore, this therapeutic strategy may represent a novel approach to combating distant metastases of breast cancer.
The purpose of the study was to conduct a systematic literature review of high-technology methods in breast cancer treatment. Material and methods. To select information sources, a global search was used using the Web of Science, Scopus, PubMed, and RSCI databases. The search included the analysis of metadata by keywords, and relevant publications were used for full-text search. The review used 55 publications from 2001 to 2021. Most of the articles were published over the past 7 years. Results. Modern literature data presented in this review prove that long-term studies based on histological and immunological features of tumor development are very important for improving survival in breast cancer. Clinical treatment protocols that were based primarily on the anatomical characteristics of the disease are now switching to the biological mechanisms underlying carcinogenesis. Drugs targeting estrogen receptors play an important role in systemic therapy and make it possible to correct the mechanisms responsible for endocrine resistance. Targeted therapy targeting the HER2 receptor, especially in an antibody-drug conjugate combination, has associated cytotoxic therapy with anti-HER2 antibodies. Modern methods of biological therapy and cell engineering make it possible to develop methods for treating triple-negative breast cancer based on the regulation of the microenvironment, mechanisms of repair, immunosuppression, and the creation of a target from a larger repertoire of both surface and intracellular antigens. Conclusion. Promising strategies based on the use of signaling and metabolic pathways, cell surface molecules, and cell engineering increase the effectiveness of treatment and improve the progression-free and overall survival in breast cancer patients.
Currently, one of the most promising approaches for the treatment of oncological patients is the selective activation of T-cell antitumor immunity using immune cells. The generation of functionally active DCs in vitro constitutes a promising approach in the development of DC-based anticancer vaccines to mobilize patient defense systems, because their activation by tumor-specific antigens to induce cytotoxic responses, and their increased efficiency of antigen presentation to induce cytotoxic T lymphocytes (CTLs) via costimulatory molecules and cytokines can be controlled. The purpose of this study was to investigate the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.