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Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: an in vivo study
Majid Asadi-Ghalehni1, Mohamad Ghaemmaghami, Alexander Klimka
1Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran , Iran and.
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.
Insights
This study explored a phage-based mimotope vaccine targeting epidermal growth factor receptor (EGFR) for cancer immunotherapy. While it induced an immune response, it showed no significant prophylactic or therapeutic advantage in reducing tumor growth.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Conventional treatments for tumors over-expressing epidermal growth factor receptor (EGFR), such as small molecule inhibitors and monoclonal antibodies (e.g., ICR-62), have limitations.
- Peptide mimotopes displayed on phage particles offer a potential alternative strategy for cancer therapy.
Purpose of the Study:
- To evaluate a phage-displayed mimotope vaccine targeting EGFR as a potential cancer immunotherapy.
- To assess the vaccine's ability to induce humoral immunity and its anti-tumor effects in a Lewis lung carcinoma mouse model.
Main Methods:
- An M13 phage displaying an ICR-62 binding peptide mimotope was constructed.
- Mice were immunized with the phage-mimotope vaccine, and humoral immunity was assessed via ELISA.
- The vaccine's prophylactic and therapeutic effects were evaluated in a Lewis lung carcinoma mouse model by measuring tumor volume.
Main Results:
- The phage-mimotope vaccine exhibited high affinity for ICR-62 and induced humoral immunity, with detectable anti-EGFR mimotope antibodies.
- A low titer of EGFR-specific antibodies was elicited, and a trend towards reduced tumor growth was observed.
- No specific prophylactic or therapeutic advantage was demonstrated in vivo.
Conclusions:
- Phage-mimotope vaccines represent a promising approach for cancer immunotherapy.
- Further research is needed to optimize this strategy for significant clinical benefit.
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