Active specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival.

TitleActive specific immunotherapy with a beta-human chorionic gonadotropin peptide vaccine in patients with metastatic colorectal cancer: antibody response is associated with improved survival.
Publication TypeJournal Article
Year of Publication2002
AuthorsMoulton HM, Yoshihara PH, Mason DH, Iversen PL, Triozzi PL
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Volume8
Issue7
Pagination2044-51
Date Published2002 Jul
ISSN1078-0432
KeywordsAdenocarcinoma, Adult, Aged, Antibodies, Neoplasm, Cancer Vaccines, Chorionic Gonadotropin, Colorectal Neoplasms, Diphtheria Toxin, Female, Humans, Immunotherapy, Male, Middle Aged, Recombinant Fusion Proteins, Safety, Survival Rate, Vaccination
Abstract

PURPOSE: 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.

EXPERIMENTAL DESIGN: 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.

Alternate JournalClin. Cancer Res.