Tumor endothelial marker 8 enhances tumor immunity in conjunction with immunization against differentiation Ag Journal Article
| Authors: | Felicetti, P.; Mennecozzi, M.; Barucca, A.; Montgomery, S.; Orlandi, F.; Manova, K.; Houghton, A. N.; Gregor, P. D.; Concetti, A.; Venanzi, F. M. |
| Article Title: | Tumor endothelial marker 8 enhances tumor immunity in conjunction with immunization against differentiation Ag |
| Abstract: | BACKGROUND: We have previously shown that xenogenic DNA vaccines encoding rat neu and melanosomal differentiation Ag induce tumor immunity. Others have developed vaccines targeting tumor neovasculature. Tumor endothelial marker 8 (TEM8) is expressed in the neovasculature of human tumors, and in the mouse melanoma B16, but its expression is limited in normal adult tissues. We describe a DNA vaccine combining xenogeneic tumor Ag and TEM8. METHODS: In-situ hybridization was used to detect TEM8 RNA in mouse tumors. Mice transgenic for the rat neu proto-oncogene were immunized with DNA vaccines encoding TEM8 and the extracellular domain of rat neu and challenged with the 233-VSGA1 breast cancer cell line. In parallel experiments, C57BL/6 mice were immunized with TEM8 and human tyrosinase-related protein 1 (hTYRP1/hgp75) and challenged with B16F10 melanoma. RESULTS: TEM8 was expressed in the stroma of transplantable mouse breast and melanoma tumors. In both model systems, TEM8 DNA had no activity as a single agent but significantly enhanced the anit-tumor immunity of neu and hTYRP1/hgp75 DNA vaccines when given in concert. The observed synergy was dependent upon CD8+ T cells, as depletion of this cell population just prior to tumor challenge obviated the effect of the TEM8 vaccine in both tumor models. DISCUSSION: A local immune responses to TEM8 may increase inflammation or tumor necrosis within the tumor, resulting in improved Ag presentation of HER2/neu and hTYRP1/hgp75. Alternatively, TEM8 expression in host APC may act more as an adjuvant than an immunologic target. |
| Keywords: | survival; survival analysis; unclassified drug; genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; animals; mice; neoplasm proteins; membrane proteins; cell differentiation; pathology; cell line, tumor; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; gene expression regulation; in situ hybridization; blotting, western; gene expression regulation, neoplastic; immunological tolerance; immunology; immune tolerance; cancer vaccine; cancer vaccines; membrane glycoproteins; recombinant proteins; membrane protein; recombinant protein; tumor protein; tumor cell line; rat; western blotting; experimental melanoma; melanoma, experimental; rats; experimental neoplasm; oxidoreductase; oxidoreductases; antigens, differentiation; cell surface receptor; differentiation antigen; receptors, cell surface; immunization; mammary neoplasms, animal; anthrax toxin receptor 1, human; tyrp1 protein, human |
| Journal Title: | Cytotherapy |
| Volume: | 9 |
| Issue: | 1 |
| ISSN: | 1465-3249 |
| Publisher: | Elsevier Science Ltd. |
| Date Published: | 2007-01-01 |
| Start Page: | 23 |
| End Page: | 34 |
| Language: | English |
| DOI: | 10.1080/14653240601048369 |
| PUBMED: | 17361485 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
29Gregor -
161Manova-Todorova -
364Houghton -
9
Orlandi
Related MSK Work