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

Clin Cancer Res. 2006 Dec 15;12(24):7389-96. doi: 10.1158/1078-0432.CCR-06-1003. Epub 2006 Nov 22.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • CD55 Antigens / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoma / immunology
  • Carcinoma / therapy*
  • Cell Proliferation
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / 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

Substances

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