title: Tecemotide: an antigen-specific cancer immunotherapy.
abstract: The identification of tumor-associated antigens (TAA) has made possible the development of antigen-specific cancer immunotherapies such as tecemotide. One of those is mucin 1 (MUC1), a cell membrane glycoprotein expressed on some epithelial tissues such as breast and lung. In cancer, MUC1 becomes overexpressed and aberrantly glycosylated, exposing the immunogenic tandem repeat units in the extracellular domain of MUC1. Designed to target tumor associated MUC1, tecemotide is being evaluated in Phase III clinical trials for treatment of unresectable stage IIIA/IIIB non-small cell lung cancer (NSCLC) as maintenance therapy following chemoradiotherapy. Additional Phase II studies in other indications are ongoing. This review discusses the preclinical and clinical development of tecemotide, ongoing preclinical studies of tecemotide in human MUC1 transgenic mouse models of breast and lung cancer, and the potential application of these models for optimizing the timing of chemoradiotherapy and tecemotide immunotherapy to achieve the best treatment outcome for patients.
authors.affiliation: a University of California , Davis; Department of Internal Medicine; Division of Hematology and Oncology ; Sacramento , CA USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wurz
authors.forename: Chiao-Jung
authors.initials: CJ
authors.lastname: Kao
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Michael W
authors.initials: MW
authors.lastname: DeGregorio
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy; D059248:Chemoradiotherapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C518273:L-BLP25; C060192:MUC1 protein, human; D008562:Membrane Glycoproteins; D018396:Mucin-1
keywords: ADT, androgen deprivation therapy; APC, antigen presenting cell; ASI, active specific immunotherapy; BSC, best supportive care; CEA, carcinoembryonic antigen; CI, confidence interval; CONSORT, consolidated standards of reporting trials; CPA, cyclophosphamide; CRT, chemoradiotherapy; CTL, Cytotoxic T-lymphocyte; Chemoradiotherapy; DMPG, Dimyristoyl phosphatidylglycerol; DPPC, Dipalmitoyl phosphatidylcholine; DTH, delayed-type hypersensitivity; ECOG, Eastern cooperative oncology group; ELISpot, enzyme-linked immunosorbent spot; FACT-L, functional assessment of cancer therapy-lung; Gy, gray; HLA, human lymphocyte antigen; HR, hazard ratio; IFN-γ, interferon gamma; IL-2, Interleukin 2; INSPIRE, stimuvax trial in Asian NSCLC patients: stimulating immune response; ITT, intent to treat; IgG, immunoglobulin G; KLH, keyhole limpet hemocyanin; LICC, L-BLP25 in colorectal cancer; LR, locoregional; MAP, multiple antigenic peptide; MHC, major histocompatibility complex; MMT, muc1-expressing mammary tumor; MPLA, monophosphoryl lipid A; MUC1; MUC1, Mucin 1; MUC1.Tg, MUC1 transgenic; NSCLC, non-small cell lung cancer; OH-BBN, N-butyl-N-(4-hydroxybutyl)nitrosamine; OS, overall survival; PBL, peripheral blood lymphocytes; PCR, pathological complete remission; PSA, prostate specific antigen; PyV-mT, polyomavirus middle-T; QOL, quality of life; RCB, residual cancer burden; RECIST, response evaluation criteria in solid tumors; RTX, radiotherapy; START, stimulating targeted antigenic responses to NSCLC; TAA, tumor associated antigen; TGF-β, transforming growth factor β; TH1, T-helper type I; TH2, T-helper type II; TNF-α, tumor necrosis factor α; TOI, trial outcome index; VNTR, variable number of tandem repeats; i.v., intravenous; immunotherapy; non-small cell lung cancer; tecemotide