title: CD8+ T-cell responses against hemoglobin-beta prevent solid tumor growth.
abstract: Bone marrow-derived dendritic cells engineered using recombinant adenovirus to secrete high levels of IL-12p70 dramatically inhibited the growth of established CMS4 sarcomas in BALB/c mice after intratumoral administration. An analysis of splenic CD8(+) T cells in regressor mice revealed a strong, complex reactivity pattern against high-performance liquid chromatography (HPLC)-resolved peptides isolated by acid elution from single-cell suspensions of surgically resected CMS4 lesions. Mass spectrometry analyses defined two major overlapping peptide species that derive from the murine hemoglobin-beta (HBB) protein within the most stimulatory HPLC fractions. Although cultured CMS4 tumor cells failed to express HBB mRNA based on reverse transcription-PCR analyses, prophylactic vaccination of BALB/c mice with vaccines containing HBB peptides promoted specific CD8(+) T-cell responses that protected mice against a subsequent challenge with CMS4 or unrelated syngeneic (HBB(neg)) tumors of divergent histology (sarcoma, carcinomas of the breast or colon). In situ imaging suggested that vaccines limit or destabilize tumor-associated vascular structures, potentially by promoting immunity against HBB+ vascular pericytes. Importantly, there were no untoward effects of vaccination with the HBB peptide on peripheral RBC numbers, RBC hemoglobin content, or vascular structures in the brain or eye.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Hideo
authors.initials: H
authors.lastname: Komita
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Taylor
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Sparvero
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Amoscato
authors.forename: Sean
authors.initials: S
authors.lastname: Alber
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Angela D
authors.initials: AD
authors.lastname: Pardee
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wesa
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D006454:Hemoglobins / Q000037:antagonists & inhibitors / Q000276:immunology*; D007111:Immunity, Cellular / Q000502:physiology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use; D014185:Transplantation, Isogeneic / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D006454:Hemoglobins; D010446:Peptide Fragments