Anti-Tumor activity of cytotoxic t lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen

Michael Wang, Pauline W. Chen, Vincenzo Bronte, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticle

Abstract

The recent cloning of tumor-associated antigens (TAAs) recognized by CD8+T lymphocytes (TCD8+) has made it possible to use recombinant and synthetic forms of TAAs to generate TCD8+with anti-tumor activity. To explore new therapeutic strategies in a mouse model, we retrovirally transduced the experimental murine tumor CT26 (H-2d), with the lacZ gene encoding our model TAA, β-galactosidase (β-gal). The transduced cell line, CT26.CL25, grew as rapidly and as lethally as the parental cell line in normal, immunocompetent animals. In an attempt to elicit TCD8+directed against our model TAA by using purely recombinant and synthetic forms of our model TAA, we synthesized a nine-amino-acid long immunodominant peptide of β-gal (TPHPARIGL), corresponding to amino acid residues 876–884, which was known to be presented by the Ldmajor histocompatibility complex (MHC) class I molecule, and a recombinant vaccinia virus encoding the full-length β-gal protein (VJS6). Splenocytes obtained from naïve mice and co-cultured with β-gal peptide could not be expanded in primary ex vivo cultures. However, mice immunized with VJS6, but not with a control recombinant vaccinia virus, yielded splenocytes that were capable of specifically lysing CT26.CL25 in vitro after co-culture with β-gal peptide. Most significantly, adoptive transfer of these cells could effectively treat mice bearing 3-day-old established pulmonary metastases. These observations show that therapeutic TCD8+directed against a model TAA could be generated by using purely recombinant and synthetic forms of this antigen. These findings point the way to a potentially useful immunotherapeutic strategy, which has been made possible by the recent cloning of immunogenic TAAs that are expressed by human malignancies.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalJournal of Immunotherapy
Volume18
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Neoplasm Antigens
Lymphocytes
Neoplasms
Vaccinia virus
Peptides
Organism Cloning
Galactosidases
Amino Acids
Cell Line
Synthetic Vaccines
Lac Operon
Adoptive Transfer
Coculture Techniques
Major Histocompatibility Complex
Neoplasm Metastasis
T-Lymphocytes
Lung
Therapeutics
Proteins

Keywords

  • Adoptive immunotherapy
  • MHC class I
  • Peptide
  • Recombinant vaccinia virus
  • T lymphocyte

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Anti-Tumor activity of cytotoxic t lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen. / Wang, Michael; Chen, Pauline W.; Bronte, Vincenzo; Rosenberg, Steven A.; Restifo, Nicholas P.

In: Journal of Immunotherapy, Vol. 18, No. 3, 1995, p. 139-146.

Research output: Contribution to journalArticle

Wang, Michael ; Chen, Pauline W. ; Bronte, Vincenzo ; Rosenberg, Steven A. ; Restifo, Nicholas P. / Anti-Tumor activity of cytotoxic t lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen. In: Journal of Immunotherapy. 1995 ; Vol. 18, No. 3. pp. 139-146.
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