This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Komita, H. Articles by Storkus, W. J. Search for Related Content PubMed PubMed Citation Articles by Komita, H. Articles by Storkus, W. J.

CD8⁺ T-Cell Responses against Hemoglobin-β Prevent Solid Tumor Growth

Departments of ¹ Dermatology, ² Surgery, ³ Pathology, ⁴ Cell Biology and Physiology, and ⁵ Immunology, University of Pittsburgh School of Medicine and ⁶ University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

Requests for reprints: Walter J. Storkus, Departments of Dermatology and Immunology, University of Pittsburgh School of Medicine, W1041.2 Biomedical Sciences Tower, 200 Lothrop Street, Pittsburgh, PA 15213. Phone: 412-648-9981; Fax: 412-383-5857; E-mail: storkuswj{at}upmc.edu.

Key Words: Interleukin-12 • Gene Therapy • Tumor • Hemoglobin-β • Pericyte

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-β (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. [Cancer Res 2008;68(19):8076–84]