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

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.

• Authors: Hong M Moulton, Paul H Yoshihara, David H Mason, Patrick L Iversen, Pierre L Triozzi
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 8 Issue 7 Pg. 2044-51 (Jul 2002) ISSN: 1078-0432 [Print] United States
• PMID: 12114402 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neoplasm
• Cancer Vaccines
• Chorionic Gonadotropin
• Diphtheria Toxin
• Recombinant Fusion Proteins
• human chorionic gonadotropin-diphtheria toxin fragment A

Topics

• Adenocarcinoma (immunology, mortality, therapy)
• Adult
• Aged
• Antibodies, Neoplasm (blood)
• Cancer Vaccines (therapeutic use)
• Chorionic Gonadotropin (immunology, therapeutic use)
• Colorectal Neoplasms (immunology, mortality, therapy)
• Diphtheria Toxin (therapeutic use)
• Female
• Humans
• Immunotherapy
• Male
• Middle Aged
• Recombinant Fusion Proteins
• Safety
• Survival Rate
• Vaccination