Tumor’s Nemesis---Dendritic Cell Vaccine

Posted by beauty33 on May 21st, 2019

Abstract: With the development of tumor biology and immunology, tumor immunotherapy has developed rapidly. Tumor immunotherapy has been seen by the clinical oncology community as an increasingly effective treatment modality over the past decade. Tumor vaccine refers to various forms of vaccines that can induce the body to produce specific T cell responses against tumors to inhibit or eliminate tumor growth, recurrence or metastasis. Due to different methods, many tumor vaccine classifications can occur. The currently accepted classification method is based on the source, target and construction vector of the tumor vaccine. Generally, tumor vaccine types include tumor cell vaccines, genetic engineering vaccines, dendritic cell vaccines, viral vaccines, polypeptide vaccines, nucleic acid vaccines, anti-unique antibody vaccines, and the like. With the in-depth study of tumor immunotherapy, it has been confirmed that dendritic cells (DC) play an important role in initiating immune response, inducing immune memory, and destroying immune tolerance, and become an important cellular tool in tumor immunology research, so the dendritic cell vaccine has become a research hotspot in recent years. With the in-depth study of DC amplification and antigen loading methods, it has become possible to start DC clinical trials in cancer patients.This article focuses on the classification of dendritic cell vaccines and their application in cancer therapy, and finally explains its future development direction and prospects.

Keywords: tumor, dendritic cell vaccine, immunotherapy

Classification of DC vaccines

Genetically modified DC vaccine

Tumor vaccines prepared by introducing target genes into DCs are currently a hot spot in tumor vaccine research, and target genes include tumor-associated antigens (TAAs) and immunomodulatory proteins such as cytokines or costimulatory molecules. There are many methods for introducing genes into DC, including cationic lipids, electroporation method, gene guns, and complexes of plasmid DNA constructed with cationic CL22, non-viral vector T7, viral vectors, and the like.

Necrotic or apoptotic load DC vaccine

DCs not only readily ingest soluble tumor antigens such as proteins or immune complexes, but also phagocytosis deadtumor cells, thereby inducing protective anti-tumor immunity. Recent comparative studies have shown that necrotic and late apoptotic cells can also trigger changes in DC maturation to induce anti-tumor immunity. DC-phagocytic necrotic tumor cells rely on the heat shock protein (HSP) they express for maturation, accompanied by up-regulation of chemical inflammatory factors and cytokines, costimulatory immune molecules, thereby inducing strong protective anti-tumor immunity in animal models. 

RNA transfected DC vaccine

Compared with traditional vaccines, DC vaccines can stimulate the body's comprehensive immune response, and the antigenic peptides expressed are close to the natural conformation and more antigenic. Moreover, mRNA is extracted from mouse tumor cell lines or from frozen sections of human tumors and can be expanded at will without losing its corresponding function. Transfection of tumor cell mRNA with DC can stimulate the versatile CTL response of tumor-bearing mice to produce protective immune markers.

Tumor antigen peptide sensitized DC vaccine

Tumor antigen peptide-sensitized DC has good targeting and experiments have shown that it can induce specific T cell responses of MHC-1 and MHC-2 both in vitro and in vivo.

Progress in clinical research of DC vaccine in the treatment of tumor

Liver cancer

DC has a powerful antigen-presenting function. As a full-time antigen-presenting cell, its main advantage lies in the activation of resting T cells, while the proportion of DC in local lymph nodes of liver cancer patients is abnormal, functional DC is significantly reduced, and the microenvironment of liver cancer formation is DC. The influence of maturation disorders makes it important to induce mature functional DCs in vitro for active immunotherapy of liver cancer. At present, the experiment uses tumor-associated antigen or tumor cell lysate, tumor-associated antigen mRNA and total RNA sensitized DC, tumor-associated antigen gene and cytokine gene transfected DC, tumor cell and DC fusion to prepare DC vaccine, and then these The sensitized DC vaccine is returned to the body to induce an effective anti-tumor immune response in the body.

Acute myeloid leukemia

Acute myeloid leukemia (AML) is a malignant tumor of hematopoietic stem/progenitor cells transformed by leukemia stem cell oncogene. Although most patients achieve complete remission under the induction of standard chemotherapy regimens, the recurrence rate remains high. Hematopoietic stem cell transplantation is currently the most effective treatment, but there are also problems of minimal residual recurrence after transplantation. Therefore, there is an urgent need to find more effective tumor treatment methods, thereby eliminating minute residual lesions and reducing leukemia recurrence.

Cellular immunotherapy represented by dendritic cells is expected to become a new method for treating tumors. Compared with other immunotherapy methods, dendritic cell immunotherapy is mainly characterized by active immunity, specificity and long duration. It can eliminate cancer stem cells or residual tumor cells in a targeted manner and exert a powerful anti-tumor immune effect.

Melanoma

Melanoma is a malignant tumor with a high degree of malignancy and rapid progression, often occurring in the skin and mucous membranes. The treatment of early melanoma mainly relies on surgery, while advanced melanoma mostly takes chemotherapy and immunotherapy, but the effect is not satisfactory. Melanoma is a highly immunogenic tumor, and melanoma is the most sensitive to biological immune cell therapy in all solid tumors. Therefore, biological immune cell therapy has been widely used in the treatment of melanoma, achieving the purpose of prolonging the survival of patients and improving the quality of life of melanoma patients. In recent years, dendritic cell vaccine reinfusion therapy has become one of the hot topics in melanoma bio immunotherapy research. In conclusion, the use of DC cell vaccines can improve the immune function of melanoma patients and prolong the progression-free survival of patients with advanced melanoma. Of course, with the continuous development and improvement of therapeutic technology, the combination of biological immune cell therapy with chemotherapy and targeted therapy may be a new trend in the future development of individualized treatment of melanoma.

DC's development prospects

DC's powerful antigen presentation function plays an important role in anti-tumor bio immunotherapy. DC-based immunotherapy is one of the most promising and valuable treatments for tumor bio immunotherapy. Existing clinical trials have shown that DC vaccine can prolong the overall survival time of some cancer patients, but there is still a gap in the clinical large-scale implementation of DC vaccine treatment, and there are many problems to be solved, and further research is needed; the preparation, storage, use and dosage of vaccines need to be further explored. It is believed that with the continuous improvement of cell therapy technology, DC-based cellular immunotherapy will give full play to its advantages of good efficacy and small adverse reactions, and play an increasingly important role in cancer therapy.

References

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[2] Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells [J]. Nat Rev Cancer, 2012, 12(4):265-278.