Colorectal Cancer Vaccines: Antiidiotypic Antibody, Recombinant Protein, and Viral Vector

Abstract

The colorectal cancer antigen GA733 (also termed CO17‐1A, KSI‐4, Ep‐CAM, KSA) has proved to be a useful target in passive immunotherapy with monoclonal antibody and in active immunotherapy with antiidiotypic antibodies in cancer patients. The GA733 antigen was molecularly cloned and expressed in baculovirus (BV), adenovirus (AV), and vaccinia virus (VV). Recombinant BV‐, VV‐, and AV‐GA733 induced antigen‐specific cytotoxic antibodies and proliferative and delayed‐type hypersensitive lymphocytes. However, only the AV recombinant induced antigen‐specific cytolytic T lymphocytes and regression of established tumors. Cured mice were protected against challenge with antigen‐negative tumors, indicating antigen spreading of immune responses. In a model of active immunotherapy against the murine homologue of the human GA733 antigen, murine epithelial glycoprotein (mEGP), BV‐derived mEGP protein in various adjuvants did not protect mice against a challenge with mEGP‐positive tumors. AV mEGP, only when combined with interleukin‐2, significantly inhibited growth of established mEGP‐positive tumors. This is in contrast to the same vaccine expressing the human antigen that was effective without interleukin‐2. AV GA733, in combination with interleukin‐2, is a candidate vaccine for colorectal cancer patients.

Quality of Recombinant Protein Determines the Amount of Autoreactivity Detected against the Tumor-Associated Epithelial Cell Adhesion Molecule Antigen: Low Frequency of Antibodies against the Natural Protein

“…Passive immunization with CO17-1A (Panorex) induced survival benefit compared with untreated patients in the clinical setting of minimal residual disease (16,17). Active immunization has been conducted using anti-Id vaccines (18 -20), recombinant protein (13,21), and viral vectors (22), but has shown limited clinical efficacy so far.…”

Novel Technologies for Vaccine Development

“…The recent licensure of DC-based vaccine Provenge ® for the treatment of prostate cancer in humans along with the approval of Oncept™ as therapy for oral melanoma in dogs lends support to the clinical promise of cancer vaccines (Aurisicchio and Ciliberto 2011). Many studies have shown that Ad-based vaccines are more efficient in generating antitumor immunity than vaccines based on other delivery systems (Basak et al 2000;Okur et al 2011). Ad vectors emerged as promising gene therapy vectors and recombinant vaccine carriers owing to their well-characterized molecular genetics, high yield propagation capacity amenable to pharmaceutical scale production, and biological characteristics (Choi and Yun 2013).…”

Genetic vaccines against Ep‐CAM break tolerance to self in a limited subset of subjects: Initial identification of predictive biomarkers

“…The low frequency of immune responders to Ep-CAM in rhesus monkeys prompted us to go back and re-examine the vaccine capability to break tolerance to self in smaller animal models in mice, where a variety of strains with well-defined MHC haplotypes are available and where it is possible to work with larger numbers of individuals [14].…”

“…To date, however, only one report has described tumor protection induced by the self mouse Ep-CAM (mEp-CAM) vaccination in the presence of a high dose of IL-2 [14].…”