Abstract
We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2kd-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a high immunogenicity to the HER-2-derived minimal CTL epitope, as shown by inducing robust CTL responses. Furthermore, the chimeric nanoparticles protected mice against HER-2-positive tumor challenge in both prophylactic and therapeutic setting. In conclusion, these results suggest that CTL epitope-carrying T7 phage nanoparticles might be a promising approach for development of T cell epitope-based cancer vaccines.
Highlights
Identification of tumor-associated antigens (TAAs) has facilitated rational design of anti-tumor vaccines
Jalali et al demonstrated that vaccination with multi-epitope peptides from the rat HER2/neu encapsulated in liposomepolycation-DNA (LPD) nanoparticles induced an antigen-specific immunity and led to lower tumor sizes and longer survival time in TUBO tumor mice model [34]
It has been previously reported that co-administration of a dominant H2-Kd-restricted CTL epitope of rat HER-2 (p66 peptide) with incomplete Freund’s adjuvant (IFA) and TLR9 agonist CpG ODN 1826 induced immune responses with prophylactic and therapeutic benefit against spontaneous mammary tumors in BALB-neuT transgenic mice [20]
Summary
Identification of tumor-associated antigens (TAAs) has facilitated rational design of anti-tumor vaccines. Most currently defined TAAs are products of self-genes overexpressed by neoplastic tissues in the body [1]. This poses a significant challenge because effective cancer vaccine strategies should be able to bypass tolerance to self-antigens. The use of the immunodominant epitopes instead of full-length proteins represents a potentially safer alternative to full-length proteins. This is advantageous when targeting self-antigens such as HER-2 that mediate key biological functions in the body, as immune responses elicited by whole protein vaccines can stimulate the growth of tumor cells if the antibodies mimic the activity of growth factor ligands. Antibodies capable of stimulating the growth of HER-2-positive tumor cells have been reported [5,6]
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