M. Wang et al., ANTITUMOR-ACTIVITY OF CYTOTOXIC T-LYMPHOCYTES ELICITED WITH RECOMBINANT AND SYNTHETIC FORMS OF A MODEL TUMOR-ASSOCIATED ANTIGEN, Journal of immunotherapy with emphasis on tumor immunology, 18(3), 1995, pp. 139-146
Citations number
54
Categorie Soggetti
Immunology,Oncology,"Medicine, Research & Experimental
The recent cloning of tumor-associated antigens (TAAs) recognized by C
D8(+) T lymphocytes (T-CD8+) has made it possible to use recombinant a
nd synthetic forms of TAAs to generate T-CD8+ with anti-tumor activity
. To explore new therapeutic strategies in a mouse model, we retrovira
lly transduced the experimental murine tumor CT26 (H-2(d)), with the l
acZ gene encoding our model TAA, beta-galactosidase (beta-gal). The tr
ansduced cell line, CT26.CL25, grew as rapidly and as lethally as the
parental cell line in normal, immunocompetent animals. In an attempt t
o elicit T-CD8+ directed against our model TAA by using purely recombi
nant and synthetic forms of our model TAA, we synthesized a nine-amino
-acid long immunodominant peptide of beta-gal (TPH-PARIGL), correspond
ing to amino acid residues 876-884, which was known to be presented by
the L(d) major histocompatibility complex (MHC) class I molecule, and
a recombinant vaccinia virus encoding the full-length beta-gal protei
n (VJS6). Splenocytes obtained from naive mice and co-cultured with be
ta-gal peptide could not be expanded in primary ex vivo cultures. Howe
ver, mice immunized with VJS6, but not with a control recombinant vacc
inia virus, yielded splenocytes that were capable of specifically lysi
ng CT26.CL25 in vitro after co-culture with beta-gal peptide. Most sig
nificantly, adoptive transfer of these cells could effectively treat m
ice bearing 3-day-old established pulmonary metastases. These observat
ions show that therapeutic T-CD8+ directed against a model TAA could b
e generated by using purely recombinant and synthetic forms of this an
tigen. These findings point the way to a potentially useful immunother
apeutic strategy, which has been made possible by the recent cloning o
f immunogenic TAAs that are expressed by human malignancies.