Development of novel HPV therapeutic vaccine constructs based on engineered exosomes and tumor cell lysates

Area of Science:

• Immunology
• Oncology
• Vaccine Development

Background:

• Human papillomavirus (HPV) infections are a global health concern, necessitating therapeutic interventions beyond current preventive vaccines.
• Existing HPV lesions and malignancies require novel treatment strategies, highlighting the need for effective therapeutic vaccines.

Purpose of the Study:

• To evaluate the immunostimulatory and anti-tumor efficacy of three distinct therapeutic HPV vaccine candidates.
• To compare the effects of recombinant protein, tumor cell lysate (TCL), and engineered exosome (Exo) platforms, all harboring the Hsp27-E7 fusion construct.

Main Methods:

• Production of recombinant Hsp27-E7 protein using an E. coli expression system.
• Generation of TCL- and Exo-based vaccine constructs (Hsp27-E7) via a lentiviral system.
• Assessment of immunological and anti-tumor effects in prophylactic and therapeutic mouse models.

Main Results:

• All three vaccine regimens (recombinant Hsp27-E7, TCL-Hsp27-E7, Exo-Hsp27-E7) induced significant anti-tumor immune responses, with identical 75% tumor-free survival rates.
• Exo-Hsp27-E7 demonstrated superior Granzyme B secretion, indicating enhanced cytotoxic T lymphocyte (CTL) activity.
• The vaccines generally promoted Th1 and CTL responses, leading to effective anti-tumor activity in the mouse model.

Conclusions:

• The engineered exosome (Exo-Hsp27-E7) vaccine candidate emerged as the most promising strategy due to higher Granzyme B levels, reduced tumor growth, and improved safety profile.
• This exosome-based therapeutic vaccine holds potential for treating existing HPV-related diseases.