Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

Abstract

Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8 + cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes.We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge.

Advancements in prophylactic and therapeutic nanovaccines

“…Another viral protein-coated dendrimer nanovaccine containing E6 and E7 peptide epitope of HPV showed enhanced cytotoxic T cell stimulation followed by HPV infected cells eradication. Tumor elimination was observed in 50% of treated mice with no recurrence up to 3 months post initial challenge [24] . Therefore, to address the problems associated with cancer vaccine development, special emphasis has been given on biomimetic personalized nanovaccines.…”

“…Vaccination provokes cell-mediated immunity generated by B cells and T cells which serve to neutralize the pathogen/antigen and simultaneously stimulating the body for developing immunological memory [24] . The CMI responses are triggered by migration of activated DCs (following uptake of nanovaccine particle) to lymphatic organs (spleen and lymph noted).…”

“…Subcutaneous vaccination with neo-antigen ADPGK nanodiscs showed enhanced CD8 + cellular response, APC uptake and increase survival after B16F10 melanoma challenge as compared to intramuscular vaccination [81] . Peptide-polymeric micelles have also been explored as a vaccine platform by conjugating hydrophilic peptide antigen with dendrimer polymers for immunotherapy [24] .…”

The application of self-assembled nanostructures in peptide-based subunit vaccine development

“…The conjugates were able to self-assemble into nanoparticles. This system has been used to deliver the following peptide antigens: B cell epitope derived from group A streptococcus M protein -J14 [69][70][71][72]; Human Papilloma Virus (HPV)-16 E7 protein epitope 8Q, and its derivatives 8Q min , 8Q Ser , 8Q Lys [73][74][75][76]. polymer 2 (Fig.…”

“…Liu et al applied a polyacrylate-based self-assembled nanoparticle delivery system to induce cellular immune responses and designed several therapeutic vaccine candidates against human papilloma virus (HPV)-related cancer (Fig. 2) [73][74][75][76]. Initially, polyacrylate 3 was chosen as a polymeric core and 8Q (QAEPDRAHYNIVTFCCKCD; E7 44−62 ) epitope from human papilloma virus (HPV-16) E7 protein as an antigen.…”