Genetic immunization with the free human chorionic gonadotropin beta subunit elicits cytotoxic T lymphocyte responses and protects against tumor formation in mice.
The free beta subunit of human chorionic gonadotropin (hCG beta) is produced and secreted by human lung, bladder, and pancreatic tumors. We attempted to generate cytotoxic T lymphocytes (CTL) with activity against free hCG beta-producing tumors by genetic immunization using a construct containing a beta subunit expressing cDNA. To assess CTL activity in vivo, a cloned syngeneic SP2/O myeloma call line was established that constitutively expresses the free hCG beta protein. Inoculation of this cell line into BALB/c mice produced large tumors within 2 weeks. However, mice immunized with the free hCG beta expression construct demonstrated a marked reduction of tumor size and weight compared with animals immunized with mock DNA ("empty" plasmid). Indeed, 30% of immunized mice were tumor-free after 3 months and thus considered long-term survivors. Inhibition of tumor growth was strongly associated with the level of CTL activity present in CD8+ cells derived from the spleen. In addition, immunized mice developed high titer anti-hCG beta antibodies that neutralized the biologic effects of the intact hCG glycoprotein hormone on its cellular receptor as well. These results illustrate that substantial cellular and humoral immune responses to the free hCG beta subunit may be generated by DNA immunization. This study thus presents a potential approach to inhibiting growth of human tumor cells that produce and secrete the free hCG beta protein.
Geissler
M
M
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Wands
G
G
Gesien
A
A
de la Monte
S
S
Bellet
D
D
Wands
J R
JR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000008:administration & dosage*
D018997:Chorionic Gonadotropin, beta Subunit, Human; D019444:Vaccines, DNA; D004247:DNA