Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

Abstract

The human colorectal carcinoma ( CRC ) -associated GA733 antigen ( Ag ), also named CO17 -1A / EpCAM / KSA / KS1 -4, has been a useful target in passive immunotherapy of CRC patients with monoclonal antibody ( mAb ) and in active immunotherapy with antiidiotypic antibodies or with recombinant protein. These approaches have targeted single epitopes ( monoclonal anti -GA733 antibodies and anti -idiotypic antibodies ) or extracellular domain epitopes ( recombinant protein ), primarily by B cells. To determine whether a reagent that induces immunity to a larger number of both B -and T -cell epitopes might represent a superior vaccine, we analyzed the capacity of full -length GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant vaccinia virus ( VV GA733 -2 ) to induce humoral, cellular, and / or protective immunity in mice. VV GA733 -2 induced Ag -specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag -positive CRC targets in conjunction with murine peritoneal macrophages as effector cells. Immunized mice developed Ag -specific, proliferative and delayed -type hypersensitive lymphocytes. VV GA733 -2 inhibited growth of ras -transformed syngeneic tumor cells expressing the human GA733 Ag in mice. These results suggest the potential of VV GA733 -2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733 -2 -expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice. The combined vaccine approach may be superior to the use of either vaccine alone in patients who are pre -immune to both viruses.

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

“…Previous reports have shown that viral vectors expressing hEp-CAM could elicit antibody as well as CTL responses in BALB/c mice [12,13]. Here we have extended these observations showing that also DNA-EP in addition to Ad-hEp-CAM vaccination elicits a cellmediated immune response.…”

“…The evaluation of human Ep-CAM (hEp-CAM) vaccines in preclinical murine models showed that vaccination with this antigen can elicit an antibody response as well as a cytotoxic T lymphocyte (CTL) response, which were associated with partial protection in tumor challenge experiments [12,13]. 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].…”

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

“…One active immunotherapy approach is using IGN101 (formulated edrecolomab) for induction of anti-Ep-CAM antiidiotypic antibodies (Zaloudik et al, 2002). This vaccination was shown to be safe, reduce Ep-CAM positive tumour cells in circulation and prolong survival of patients with metastatic rectal cancer (Himmler et al, 2005).…”

Anti-inflammatory actions of plant-derived multiple monoclonal antibody CO17-1A × BR55 related with anti-cancer effects in AOM/DSS-induced colorectal cancer mouse via down-regulating of ERK1/2

“…CO17-1A, a human CRC-associated antigen, is highly expressed in CRC patients (Zaloudik et al 2002). Several studies reported the anti-cancer effects of antiEpCAM in colorectal cancer growth (Ko et al 2005;Kwak et al 2011).…”