Why tumor immunotherapy is listed as one of the most promising scientific fields?
Tumor always annoys human's health. With the biologically complex, diverse and variable, the understanding on tumor development mechanism and cure ways are great challenges for scientists. Since 1890s when Coley designed the first bacterial-based tumor vaccine till1970s and 1980s when people explored on antibody therapy and cytokine therapy, to 2010 FDA approved the first cell immunotherapy for prostate cancer, tumor immunotherapy has experienced more than 100 years of development and progress. Especially in recent years, people have further understanding on the relation between tumor and host, especially the anti-tumor immune response and tumor immune escape mechanism. Immune cells, molecules and gene-based interventions are scientists' hit point and have got exciting results on clinical trials. In addition to surgery, radiotherapy and chemotherapy for cancer treatments, tumor immunotherapy has been clarified as the fourth category as well as significant clinical effect and advantage. In clinical work, immunotherapy has been successfully applied to prostate cancer, melanoma, lymphoma, breast cancer, lung cancer and other tumors; it significantly improved patients' life quality. With new principle and new method exploring, various immunotherapy and therapy combinations will bring leap for the field of science. It can predict that immunotherapy in the near future will make a significant contribution to anti-tumor and improve life quality.
What methods tumor immunotherapy contain? On the terms of the immune cells selection, genetic engineering and tumor immune escape handle, does tumor immunotherapy have new cutting-edge technology?
Tumor immunotherapy is divided into active immunotherapy and passive immunotherapy based on whether it initiatively promotes the anti-tumor immune response, the former, such as tumor vaccines, the latter, which primarily consist of antibodies, killer cells and cytokines (such as interferon, interleukin, colony-stimulating factor) etc. Tumor vaccines, including cell-based vaccine, peptide-based vaccine and nucleic acid-based vaccine and others, promote body's anti-tumor-specific immune response through extracting tumor antigen for immunization.
Dendritic cell (DC)-based vaccine has made breakthrough in clinical studies on tumor immunotherapy, and become a hot research field. DC vaccine introduces the tumor antigen carrying DC into in vitro, these DCs mediate tumor destruction through antigen presentation and cytokines secretion to regulate tumor antigen-specific Th1 cell activation and proliferation and further promote the activation of NK cells and CTL. However, in certain circumstances, the (immature or non-adjustable) DC in vivo may also promote Th17, Th2 and Treg cells generating, which could cause adverse effect of promoting tumor growth in body. Thus how selectively "go after profits and avoid disadvantages" has become the main challenges of DC vaccine. Studies have shown that type I/II-type interferon in combination with TNF-α or TLR ligand stimulating induced DC1 is effective in inducing Th1-type response, in which activated DC has entered many clinical trials in multiple tumor treatment.
Targeted tumor protein and peptide vaccine was proved to be able to stimulate CD4 + and CD8 + T-cell activation, however, its limited immune response activating effect darken its role in anti-tumor. Currently, one of the main hotspots of this area is the effect of TLR ligand on peptide vaccine adjuvant. Studies have shown that TLR ligands (TLR3 ligand, TLR4 ligands, TLR7/8 ligand and TLR9 ligand) as an adjuvant with peptide vaccine can mediate tumor cell death via promoting APC and NK cell activity. Adding PD-1 and TIM-3 blocking antibody onto CPG adjuvant peptide vaccine may enhance T cell immune response induced by the vaccine, and weaken the tumor-induced T cell inactivation thus to overcome tumor escape.
Genetic engineering strategy combining with tumor immunotherapy also shows prospects in clinical practice. Introduce the targeted gene vectors such as a plasmid or viral (retrovirus, lentivirus, adenovirus, vaccinia virus) into the body, through the extraction of APC and antigen presentation to activate cellular anti-tumor antigen and humoral immune response (HI). How to enhance the exogenous gene triggered immune response are the technical difficulties of nucleic acid-based vaccines. Studies have shown that the co-introduction of IL-2 or IL-12 expression plasmid can enhance the anti-tumor effect of the DNA vaccine. Another method is to introduce the recombinant expression vector into autologous tumor cells to enhance the immune response. Enhance the immunogenicity of the DNA vaccine on the one hand can simultaneously introduce genes expression of immune stimulating molecules such as GM-CSF or CD40L, on the other hand by Prime-boost strategy. Studies have shown that using plasmid DNA initialize T cell immune response, and then using viral DNA to strengthen the immune response, this gene immunotherapy, has shown a good efficacy in the treatment of experimental tumors.
At present, do the domestic and foreign markets have relative mature products?
From 1995, the first FDA approved cancer immunotherapy drug IFN-α2, Roferon-A for the treatment of grade IIB/III melanoma, the tumor immunotherapy drugs or therapies have got great development in recent years. In 2004, the FDA approved the first anti-angiogenesis drugs, anti-VEGF monoclonal antibody Avastin as the first-line treatment for metastatic colorectal cancer, later the approval was expanded to the treatment of non-small cell lung cancer, renal cell carcinoma and HER2-negative breast cancer. In 2010, Provenge production by the U.S. Dendreon became the first cancer vaccine that formally listed and approved by the FDA, Provenge is a self-DC presentation tumor antigen peptide vaccine for advanced prostate cancer patients especially failure of hormone therapy. In 2011, the FDA approved the listing of Ipilimumab as a specificity of human CTLA4 monoclonal antibodies for the treatment of advanced melanoma. These are the examples of major breakthrough in the history of tumor immunotherapy, which not only encourage tumor immunotherapy R&D staff, but also enhance people's confidence to overcome tumor.
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