title: Optimal epitope composition after antigen screening using a live bacterial delivery vector: application to TRP-2.
abstract: Immunotherapeutic approaches, based on the generation of tumor-specific cytotoxic T-lymphocytes (CTL), are currently emerging as promising strategies of anti-tumor therapy. The potential use of attenuated bacteria as engineered vectors for vaccine development offers several advantages, including the stimulation of innate immunity. We developed an attenuated live bacterial vector using the type III secretion system (TTSS) of Pseudomonas aeruginosa to deliver in vivo tumor antigens. Using an inducible and rapid expression plasmid, vaccination with several antigens of different length and epitope composition, including TRp-2, gp100 and MUC18, was evaluated against glioma tumor cells. We observed similar CTL immunity and T-cell receptor (TCR) repertoire diversity with the vaccines, TRP2(125-243), TRP2L(125-376) and TRP2S(291-376). However, only immunization with TRP2L(125-376) induced significant anti-tumor immunity. Taken together, our data indicate the importance of the epitopes composition and/or peptide length of these peptides for inducing cytotoxic T-lymphocyte (CTL) mediated immunity. Characteristics that consistently improved anti-tumor immunity include: long peptides with immunodominant and cryptic CD8(+) epitopes, and strong CD4(+) Th epitopes. Our bacterial vector is versatile, easy-to-use and quick to produce. This vector is suitable for rapid screening and evaluation of antigens of varying length and epitope composition.
authors.affiliation: Therex, TIMC-IMAG, CNRS Université Joseph Fourier; La Tronche, France.
authors.forename: Madiha
authors.initials: M
authors.lastname: Derouazi
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Raphaël
authors.initials: R
authors.lastname: Marlu
authors.forename: Olivier
authors.initials: O
authors.lastname: Epaulard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mayol
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pasqual
authors.forename: Audrey
authors.initials: A
authors.lastname: Le Gouellec
authors.forename: Benoit
authors.initials: B
authors.lastname: Polack
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toussaint
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D057005:Bioengineering; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000008:administration & dosage / Q000235:genetics*; D005260:Female; D005818:Genetic Engineering; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology / Q000628:therapy; D007167:Immunotherapy; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D017931:DNA Primers; D000939:Epitopes; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase