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 language | English (US) |
|---|---|
| Pages (from-to) | 139-146 |
| Number of pages | 8 |
| Journal | Journal of Immunotherapy |
| Volume | 18 |
| Issue number | 3 |
| State | Published - 1995 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Anti-Tumor activity of cytotoxic t lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen
AU - Wang, Michael
AU - Chen, Pauline W.
AU - Bronte, Vincenzo
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 1995
Y1 - 1995
N2 - 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.
AB - 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.
KW - Adoptive immunotherapy
KW - MHC class I
KW - Peptide
KW - Recombinant vaccinia virus
KW - T lymphocyte
UR - http://www.scopus.com/inward/record.url?scp=0029608953&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029608953&partnerID=8YFLogxK
M3 - Article
C2 - 8770769
AN - SCOPUS:0029608953
VL - 18
SP - 139
EP - 146
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1524-9557
IS - 3
ER -