Immunization with Mimotopes Prevents Growth of Carcinoembryonic Antigen–Positive Tumors in BALB/c Mice

Abstract

Purpose: The carcinoembryonic antigen (CEA) is a glycoprotein that is overexpressed in nearly 50% of all human and veterinarian tumors. At present, anti-CEA antibodies are being tested in clinical studies as passive immunotherapeutics. This study aims to establish an active immunotherapy for the poorly immunogenic CEA glycoprotein by generating antigen surrogates. Experimental Design: We used the monoclonal anti-CEA antibody Col-1 and the biopanning method to generate peptide mimics (mimotopes) of the Col-1epitope. The peptide showing the highest specificity and mimicry was synthesized as an octameric multiple antigenic mimotope (MAM). Subsequently, immunogenicity of the selected mimotope was examined in BALB/c mice.We assessed antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity mediated by the induced antibodies on CEA-expressing HT29 tumor cells. Furthermore, after immunization, the BALB/c mice were transplanted s.c. with Meth-A/CEA tumor cells. Results: When BALB/c mice were immunized with this MAM, they generated a specific humoral immune response against CEA. The mimotope-induced polyclonal and poly-isotypic antibodies induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro. Furthermore, when MAM-immunized mice were transplanted s.c. with Meth-A/CEA cells expressing human CEA, a suppressed tumor growth was observed. Conclusion: From our results, we can conclude that the Col-1 epitope of the glycoprotein CEA can be translated into an immunogenic peptide mimic. The mimotope-induced antibodies recognize CEA and do effectively inhibit growth of CEA-positive tumors. Based on these finding, we suggest that the generated mimotopes are candidates for active immunotherapy of CEA-expressing tumors.

Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: anin vivostudy

“…In order to be rendered immunogenic, these peptides are coupled to carrier proteins 19 or designed into multi-mimotope constructs 20 . In the present study, using genetic-based carrier system, we developed a filamentous bacteriophage-based vaccine displaying EGFR mimotopes on pVIII, and evaluated its effectiveness both in vitro and in vivo.…”

Soluble Carcinoembryonic Antigen Activates Endothelial Cells and Tumor Angiogenesis

“…Initially, we were referred to a potential role of CEA in tumor angiogenesis by a recent immunologic CEA-targeting study (16). Thereby, CEA-vaccinated mice were found to have a remarkably lower degree of vascularization in tumors of CEA-immunized mice, as compared with tumors in control animals ( Supplementary Fig.…”

“…In a previous study, CEA was immunologically targeted via CEA mimotope vaccination, resulting in a significantly reduced growth of CEA-expressing tumor transplants (Meth-A/CEA; ref. 16). Although in CEA mimotope-vaccinated mice tumor angiogenesis was markedly reduced (Supplementary Fig.…”

“…We were referred to a potential paracrine function of CEA in a previous CEA-mimotope immunization study (16). In this particular study, CEA was the immunologic target of a CEA-directed mimotope vaccination, resulting in a significantly reduced growth of CEA-expressing tumor transplants (Meth-A/CEA).…”

A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization

“…Therefore, they are able to prevent the high-affinity interaction between allergen and specific IgE antibodies [3,8] and thus can be called blocking antibodies [9,10]. In several studies we and others have already characterized peptides and anti-idiotypic Fab fragments being mimotopes of different allergens and antigens [2,6,[11][12][13].…”