A neoadjuvant/adjuvant randomized trial of colorectal cancer patients vaccinated with an anti-idiotypic antibody, 105AD7, mimicking CD55.

Abstract

PURPOSE:

To assess the tolerability and effectiveness of 105AD7 vaccination in colorectal cancer patients. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein, which is more than expressed on colorectal cancer cells and protects them from attack by complement.

EXPERIMENTAL DESIGN:

Colorectal cancer patients (n = 67) eligible for primary surgery were randomized to receive the anti-idiotypic antibody 105AD7+/-Bacillus Calmette-Guerin/alum or to no treatment (control group). The immunizations were given i.d./i.m. before surgery and continued for a period of 2 years. The patients were monitored in enzyme-linked immunospot (ELISPOT; gamma-IFN), proliferation assay, and Luminex cytokine assays.

RESULTS:

No serious adverse events were recorded. Of the 32 investigated immunized patients, 14 (44%) were considered to be responders in the ELISPOT assay. Induced proliferative responses were noted in 17 of 40 (43%) monitored patients. There was no correlation between the ELISPOT and proliferation assays. Luminex analyses revealed tumor necrosis factor-alpha and granulocyte macrophage colony-stimulating factor responses not only to the vaccine but also toward the native antigen CD55 in 9 of 13 (69%) patients.

CONCLUSIONS:

Immune responses to vaccination were induced in a majority of monitored patients measured by ELISPOT and proliferation assay. The lack of correlation between the ELISPOT and proliferation assays may reflect the fact that the two methods measure different T-cell responses and highlights the importance of multiple readouts in evaluating a potential cancer vaccine. Responses to both the anti-idiotype and the CD55 antigen were measurable, adding support to the use of CD55 as a target in cancer treatment.

• Authors: Gustav J Ullenhag, Ian Spendlove, Nicholas F S Watson, Adrian A Indar, Mukul Dube, Richard A Robins, Charles Maxwell-Armstrong, John H Scholefield, Lindy G Durrant
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 24 Pg. 7389-96 (Dec 15 2006) ISSN: 1078-0432 [Print] United States
• PMID: 17121873 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 105AD7 antibody
• Adjuvants, Immunologic
• Antibodies, Anti-Idiotypic
• CD55 Antigens
• Cancer Vaccines
• Cytokines
• Interferon-gamma

Topics

• Adjuvants, Immunologic (therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Anti-Idiotypic (therapeutic use)
• CD55 Antigens (immunology)
• Cancer Vaccines (therapeutic use)
• Carcinoma (immunology, therapy)
• Cell Proliferation
• Colorectal Neoplasms (immunology, therapy)
• Cytokines (blood)
• Female
• Humans
• Immunization, Passive (methods)
• Interferon-gamma (blood)
• Lymphocyte Activation (immunology)
• Male
• Middle Aged
• Molecular Mimicry (immunology)
• Neoadjuvant Therapy
• T-Lymphocytes (immunology)
• Treatment Outcome