Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen

Ken Yu Lin, Frank G. Guarnieri, Kevin F. Staveley-O'Carroll, Hyam I. Levitsky, J. Thomas August, Drew M. Pardoll, Tzyy Choou Wu

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Abstract

Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity. In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP- 1). Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7. In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All mice vaccinated with 1 x 107 plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection. Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC- 1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden. These findings point out the therapeutic limitations of recombinant vaccinia expressing unmodified tumor antigens. Further, they demonstrate that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.

Original languageEnglish (US)
Pages (from-to)21-26
Number of pages6
JournalCancer Research
Volume56
Issue number1
StatePublished - Jan 1 1996

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Vaccinia
Histocompatibility
Neoplasm Antigens
Vaccines
Neoplasms
Human papillomavirus 16
Therapeutics
Papillomaviridae
Lysosome-Associated Membrane Glycoproteins
Vaccine Potency
T-Lymphocytes
CD4 Antigens
Synthetic Vaccines
ras Genes
Histocompatibility Antigens Class II
Antigen Presentation
Tumor Burden
Inbred C57BL Mouse
Immunity
Epithelial Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lin, K. Y., Guarnieri, F. G., Staveley-O'Carroll, K. F., Levitsky, H. I., August, J. T., Pardoll, D. M., & Wu, T. C. (1996). Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Research, 56(1), 21-26.

Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. / Lin, Ken Yu; Guarnieri, Frank G.; Staveley-O'Carroll, Kevin F.; Levitsky, Hyam I.; August, J. Thomas; Pardoll, Drew M.; Wu, Tzyy Choou.

In: Cancer Research, Vol. 56, No. 1, 01.01.1996, p. 21-26.

Research output: Contribution to journalArticle

Lin, KY, Guarnieri, FG, Staveley-O'Carroll, KF, Levitsky, HI, August, JT, Pardoll, DM & Wu, TC 1996, 'Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen', Cancer Research, vol. 56, no. 1, pp. 21-26.
Lin KY, Guarnieri FG, Staveley-O'Carroll KF, Levitsky HI, August JT, Pardoll DM et al. Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Research. 1996 Jan 1;56(1):21-26.
Lin, Ken Yu ; Guarnieri, Frank G. ; Staveley-O'Carroll, Kevin F. ; Levitsky, Hyam I. ; August, J. Thomas ; Pardoll, Drew M. ; Wu, Tzyy Choou. / Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. In: Cancer Research. 1996 ; Vol. 56, No. 1. pp. 21-26.
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