Active specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival.
OBJECTIVE
Human chorionic gonadotropin (hCG) is produced by colorectalcancers and may play a role in its progression. The clinical and immunological effects of a synthetic vaccine targeting beta-hCG composed of the COOH terminal peptide of beta-hCG (CTP37) conjugated to diphtheria toxoid (DT) was investigated in patients with metastatic colorectal cancer.


METHODS
Seventy-seven patients from 12 centers were randomly divided into two vaccine dose groups. CTP37-DT was formulated in an emulsion and administered i.m. on days 0, 28, and 70. Patients were evaluated for toxicity, overall survival, and antibody response to hCG and to DT.


RESULTS
Immunizations were well tolerated with no patients requiring cessation of the injections. Anti-hCG antibody was detected in 56 of the 77 patients treated. Significant differences in antibody response and survival were not observed between the two dose groups. An intention-to-treat analysis of all vaccinated patients showed a median survival of 34 weeks. Patients who developed anti-hCG antibody levels higher than or equal to the median value exhibited a median survival of 45 weeks compared with 24 weeks for patients who developed anti-hCG antibody levels lower than the median (P = 0.0002). In contrast, no significant difference was observed when comparing survival based upon the level of DT antibody that developed (P = 0.80).


CONCLUSIONS
Vaccination with CTP37-DT induced anti-hCG antibodies in most patients with advanced colorectal cancer. Anti-hCG antibody induction was associated with longer overall survival. CTP37-DT has an excellent safety profile and warrants further study in patients with colorectal cancer.
Moulton
Hong M
HM
AVI BioPharma, Inc., Portland, Oregon 97258, USA. moulton@avibio.com
Yoshihara
Paul H
PH
Mason
David H
DH
Iversen
Patrick L
PL
Triozzi
Pierre L
PL
D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006063:Chorionic Gonadotropin / Q000276:immunology* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins; D012449:Safety; D015996:Survival Rate; D014611:Vaccination
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D006063:Chorionic Gonadotropin; D004167:Diphtheria Toxin; D011993:Recombinant Fusion Proteins; C047471:human chorionic gonadotropin-diphtheria toxin fragment A