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

Abstract

To date, several small molecule inhibitors and monoclonal-antibodies (like ICR-62) have been used to treat tumors over-expressing epidermal growth factor receptor (EGFR). However, the limitations associated with these conventional applications accentuate the necessity of alternative approaches. Mimotopes as compelling molecular tools could rationally be employed to circumvent these drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide mimotope is exploited as a vaccine candidate. It exhibited high affinity towards ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization, phage-based mimotope vaccine induced humoral immunity. Elicited anti-EGFR mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine was tested on the Lewis lung carcinoma mice model to investigate the prophylactic and therapeutic effects. The tumor volume was measured and recorded in different animal groups to evaluate the anti-tumor effects of the vaccine. Our data indicate that the reported phage-based mimotope could potentially elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth. However, in vivo experiments of prophylactic or therapeutic vaccination showed no specific advantage. Furthermore, phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy.

The Immunogenicity and Anti-Tumor Efficacy of a Rationally Designed EGFR Vaccine

“…Active immunization with tumor specific antigens or epitopes formulated with strong adjuvants such as complete Freund’s adjuvant (CFA) has been shown therapeutic effect on a number of cancer types [12-14]. The ECD of mouse EGFR is responsible for ligand binding and the receptor dimerization, and is composed of four structural sub-domains, among which the sub-domain II (aa190-334) is responsible for the receptor dimerization, and the sub-domain III (aa335-506) is responsible for the ligand-binding [15].…”

Identification of Clonal Neoantigens Derived From Driver Mutations in an EGFR-Mutated Lung Cancer Patient Benefitting From Anti-PD-1

“…We presented a pipeline combining in silico and in vitro approaches to identify true neoantigens. Neoantigens expressed by a large proportion of tumor cells were defined as clonal neoantigens (34). In contrast, subclonal neoantigens may be generated during tumor evolution, which mediated immune escape and facilitated tumor invasion (35).…”

“…Here, a total of four clonal neoantigens, including two arising from EGFR 19del, 1 from TP53 A161T, and 1 from DENND6B R398Q, respectively, were validated in this case. Although immunotherapy targeting EGFR mutations have been widely discussed (34), there was no research on identifying neoantigens generated from EGFR mutations in NSCLC patients. Neoantigens derived from hotspot mutations of TP53, the most frequently altered gene across solid tumors, have already been screened for novel therapeutic approaches (35).…”

Phage antibodies for the immunochemical characterization of Herbaspirillum seropedicae Z78 glycopolymers

“…The problem is solved with antibodies based on variable antigen-binding fragments that are obtained from antibody fragment libraries by phage display (MacCafferty et al 1990). The most commonly used are Fab and scFv fragment libraries, in which the antigen-binding fragment is present at the surface of bacteriophage M13 as part of its pIII protein (miniantibodies (miniAbs) in phage format) (Asadi-Ghalehni et al 2015;Petrenko 2018). Phage display technology, proposed by Smith (Smith 1985;MacCafferty et al 1990;Smith and Petrenko 1997), replaces all work stages with simple manipulations with DNA and bacteria, yielding stable antibodyproducing clones within weeks rather than months and decreasing the associated costs.…”