Tumor Biotherapy

Biotherapy is a new therapy for tumor prevention and treatment by applying modern biotechnology and its products, which can achieve anti-tumor effect by mobilizing the natural defense mechanism of the host or giving natural (or genetically engineered) produced substances with strong targeting properties. With the in-depth research on the molecular mechanism of tumorigenesis and development and the development of biotechnology, biotherapy has become the fourth mode in the comprehensive treatment of tumors, and has received more and more attention. It has become the most remarkable and inspiring focus at the 37th to 40th American Society of Clinical Oncology (ASCO) and the 7th China Society of Oncology (CSCO). Tumor biotherapy now mainly includes: somatic cell therapy and cytokine therapy, tumor vaccine and dendritic cells, tumor molecular targeted therapy, radioimmunotargeted therapy, tumor gene therapy and biochemotherapy. Jing Liang, Department of Tumor Chemotherapy, Thousand Buddha Mountain Hospital, Shandong Province, China 1 Somatic cell therapy and cytokine therapy Somatic cell therapy is to obtain the patient’s own immune cells by isolation, and under the induction of cytokines, a large number of highly anti-tumor activity of immune cells are expanded, and then infused back into the patient’s body. These cells include LAK cells, TIL cells, CIK cells, DC cells and CD3AK cells, etc. This therapy is highly effective in treating a variety of tumors such as malignant melanoma, kidney cancer, non-Hodgkin’s lymphoma, and cancerous pleural and abdominal fluid, and the toxic side effects are mild. Cytokines are small peptide molecules synthesized and secreted by activated immune cells (monocytes/macrophages, T cells, B cells, NK cells, etc.) or mesenchymal stromal cells (vascular endothelial cells, epidermal cells, fibroblasts, etc.), and they have the functions of regulating cell growth, differentiation and maturation, regulating immune response, participating in inflammation, promoting wound healing and participating in the growth and development of tumors. Clinical applications include interferon (IFN-α, IFN-β, IFN-γ), interleukin (IL-2, IL-4, IL-7, IL-12, etc.), hematopoietic stimulating factor (EPO, TPO, G-CSF, GM-CSF, IL-11, IL-3, etc.), tumor necrosis factor (TNF-α), repair factors (GM1, EGF, BFGF, etc.), BFGF, etc.). It is used in the treatment of leukemia, lymphoma, solid tumors, viral infections, hematopoietic inhibition, and radiation damage. Somatic cell therapy and cytokine therapy are often complementary, taking a more combined application. Such as CIK/IL-2 combination, TIL/IL-2 combination, LAK/IL-2 combination, DC/IL-2/IFN-γ combination, IL-2/IFN-α/TFN-α combination, etc., especially can be used for hematopoietic stem cell directed differentiation and expansion. These therapies have now been clinically applied for many years and have achieved better efficacy. 2 Tumor vaccines and dendritic cells Dendritic cells (DCs) are the most effective antigen-presenting cells in the human body, and in recent years DCs have become one of the hotspots that have attracted much attention in today’s field of tumor biotherapy, with more and more evidence indicating that cellular immunity activated by DCs, especially cytotoxic T lymphocyte (CTL)-mediated immune responses, plays a significant role in the body’s defense against The preparation of DC vaccines includes direct stimulation of DCs with tumor antigenic peptides or proteins, stimulation of DCs with tumor tissue protein extracts, and transfection of DCs with antigenic and cytokine genes. Among them, antigen gene transfection of DC or cytokine gene transfection of DC can make antigen molecules and cytokines stably expressed in DC for a long period of time, so it has better stimulation effect. 3 Molecularly targeted therapy Another major advance in tumor biotherapy is the successful application of molecularly targeted therapeutic agents, which are mainly of two types: monoclonal antibodies and small molecule compounds of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI). The monoclonal antibody class of molecularly targeted drugs are commonly used: trastuzumab (trastuzummab, Herceptin), rituximab (rituxan, Merovax), cetuximab (cetuximab, IMC-C225, Ebixol), and bevacizumab (Avastin), etc.; and the small-molecule compounds are commonly used: glivec ( STI571, imatinib, Gleevec), Iressa (ZD1839, gefitinib, Iressa), and Tarceva (OSI774, Trocar). The implementation of molecularly targeted therapy first requires finding the correct molecular target through techniques such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and screening for appropriate targeted drugs based on their results, which can be treated with simple biotherapy, biochemotherapy, bioradiotherapy, and other modalities. After completing a certain course of treatment and medication, the efficacy will be evaluated by PET/CT, CT, MRI and tumor markers, etc. Attention will be paid to dosage reduction and maintenance during the treatment process, and close follow-up will be carried out. 4 Gene therapy The use of cell engineering technology to introduce exogenous target genes into human target cells or tissues in order to replace defective genes and achieve the purpose of preventing and treating tumors through their normal expression. The basic strategies of tumor gene therapy mainly include the following ways: gene replacement, gene modification, gene addition, gene supplementation, gene closure and so on. It is divided into in vivo gene therapy and in vitro gene therapy according to the different ways of functional gene introduction. Viruses are commonly used as carriers to deliver genes, and gene-transduced P53 (e.g., AV-P53), gene-transduced DC (e.g., AAV-BA46-DC), and gene-transduced TIL (IL-2 and TNF-α) have been used in various phases of clinical studies, and their efficacy is subject to further clinical evaluation. 5 Biochemotherapy Biotherapy is based on the cutting-edge science of modern molecular biology, cell biology and molecular immunology, emphasizing the molecular basis of tumor development and transmutation and the pertinence, specificity (targeting) and effectiveness of treatment. It has definite efficacy when applied alone, and may increase the efficacy when applied at the same time or in sequence with other therapeutic means; it mostly has no negative impact and obvious toxicity on normal hematopoietic, immune and major organ functions. Chemotherapy is generally a cytotoxic drug with poor targeting, which significantly affects patients’ hematopoiesis, immunity and function of certain organs (systems) while killing tumor cells, and is prone to multi-drug resistance and failure. Tumor biochemotherapy is a new comprehensive treatment mode in which biotherapy and chemotherapy are jointly applied in tumor treatment, which is based on the pathological type, clinical staging, site of occurrence and development trend of the tumor, combined with the patient’s systemic condition and molecular biological behavior, and systematically applying chemotherapeutic drugs and biologics in combination to achieve the best therapeutic effect and improve the quality of survival. Some successful biochemotherapy regimens have been applied in the clinic, such as NSCLC can be treated with Iressa+GEM, CD20-positive B-cell NHL can be treated with Rituximab+CHOP, Her-2-positive breast cancer can be treated with Herceptin+TAX/NVB, colorectal cancer can be treated with IMC-C225+CPT-11, and these regimens have achieved better These regimens have achieved good therapeutic effects. 6 Conclusion The integrated application of the existing possible methods to treat tumors has been deeply rooted in people’s minds and accepted by oncology clinicians. The joint cooperation between surgery, chemotherapy, radiotherapy and biotherapy has achieved remarkable efficacy in the treatment of a wide range of tumors. This concept emphasizes both the organism and the disease, and stresses that there should be a planned and rational combination of biotherapy and other treatments to improve the efficacy and prolong the survival time on the one hand, and to improve the patient’s lifestyle and quality of life on the other. Some of the modalities that are indeed feasible include: biochemotherapy (Herceptin+Taxol/GEM/NVB); molecularly targeted therapy combined with immunotherapy (Iressa-CIK/IL-2); biotherapy combined with endocrine therapy (Herceptin+TAM); biotherapy combined with TCM (Iressa+Chinese herbal medicine to identify the symptoms and treat the disease); and bioradiotherapy ( IMC225+radiotherapy). In conclusion, biotherapy has become an important means of tumor treatment in the 21st century, and how to better combine biotherapy with other therapeutic means to improve the therapeutic effect and the quality of survival will undoubtedly help biotherapy to play the most important role in the comprehensive treatment of tumors.