title: Therapeutic gene modified cell based cancer vaccines.
abstract: History of cancer immunotherapy lasts for more than 120 years. In 1891 William B. Coley injected bacteria into inoperable cancer (bone sarcoma) and observed tumor shrinkage. He is recognized as the "'"Father of Immunotherapy"'". Cancer immunotherapy is based on the ability of the immune system to recognize cancer cells and to affect their growth and expansion. Beside the fact that, tumor cells are genetically distinct from their normal counterparts, and should be recognized and eliminated by immune system, the tumor associated antigens (TAAs) are often poorly immunogenic due to immunoediting. This process allows tumor to evolve during continuous interactions with the host immune system, and eventually escape from immune surveillance. Furthermore, tumor microenvironment consists of immunosuppressive cells that release immunosuppressive factors including IL-6, IL-10, IDO, TGFβ or VEGF. Interactions between cancer and stroma cells create network of immunosuppressive pathways, while activation of immune defense is inhibited. A key to successful immunotherapy is to overcome the local immunosuppression within tumor microenvironment and activate mechanisms that lead to tumor eradication. There are two clinical approaches of immunotherapy: active and passive. Active immunotherapy involves stimulation of immune response to tumor associated antigens (TAAs), either non-specifically via immunomodulating agents or specifically employing cancer vaccines. This review presents the progress and breakthroughs in design, development and clinical application of selected cell-based tumor vaccines achieved due to the generation and development of gene transfer technologies.
authors.affiliation: Department of Cancer Immunology, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kozłowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Mackiewicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Mackiewicz
mesh_terms: D019496:Cancer Vaccines / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D014411:Neoplastic Stem Cells / Q000276:immunology; D014020:Tissue Extracts / Q000627:therapeutic use; D059016:Tumor Microenvironment / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; C464842:Canvaxin; C116434:Melacine; D014020:Tissue Extracts; D019444:Vaccines, DNA; C511774:sipuleucel-T
keywords: (CD80) cluster of differentiation 80; AAV; ABCB5+; ALDH; AML; APCs; ATP-binding cassette sub-family B member 5; Ad6; B7.1; BCG; Bacillus Calmette-Guérin vaccine; CMV; CSCs; CTLA-4; DCs; DNA; EGT; GM-CSF; GMTV; Genetically modified tumor vaccines; H6; HER2/neu; HIV-1; HLA; HPV; ICAM-1; IDO; IFNά; IFNγ; IL-10; IL-12; IL-15; IL-2; IL-4; IL-6; IL-7; Immunotherapy; JAK; Janus kinase; LFA-3; MAGE; MAPK; MART-1; MDSCs; MHC; MSCs; MoMLV; Moloney murine leukemia virus; NK cells; OS; PD-1; PI3K; RECIST; RNA; Response Evaluation Criteria in Solid Tumors; SIV; SSEA-1; STAT; T regulatory cells; T-cell immunoglobulin domain and mucin domain 3; T-cell immunoglobulin domain and mucin domain 4; T-regs; TAAs; TAMs; TGFβ; TIM-3; TIM-4; Therapeutic cancer vaccines; VEGF; acute myeloid leukemia; adeno-associated viruses; adenovirus serotype 6; aldehyde dehydrogenase; antigen presenting cells; cDNA; cancer stem cells; complementary DNA; cytomegalovirus; cytotoxic T-lymphocyte antigen 4; dendritic cells; deoxyribonucleic acid; electro-gen-transfer; genetically modified tumor vaccine; glycoprotein 100; glycoprotein 130; gp100; gp130; granulocyte-macrophage colony-stimulating factor; hTERT; human epidermal growth factor receptor 2; human immunodeficiency virus 1; human leukocyte antigen; human papillomavirus; human simian immunodeficiency virus; human telomerase; hyper interleukin 6; indoleamine-pyrrole 2,3-dioxygenase; intercellular adhesion molecule 1; interferon alpha; interferon gamma; interleukin 10; interleukin 12; interleukin 15; interleukin 2; interleukin 4; interleukin 6; interleukin 7; lymphocyte function-associated antigen 3; major histocompatibility complex; melanoma antigen recognized by T-cells 1; melanoma stem cells; melanoma-associated antigen; mitogen-activated protein kinase; myeloid-derived suppressor cells; natural killer cells; overall survival; phosphatidylinositide 3-kinase; programmed cell death protein 1; ribonucleic acid; short interfering RNA; siRNA; signal transducer and activator of transcription; stage-specific embryonic antigen 1; transforming growth factor beta; tumor associated antigens; tumor-associated macrophages; vascular endothelial growth factor