Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell Immunity

Area of Science:

• Immunology
• Vaccinology
• Oncology

Background:

• Human papillomavirus (HPV) infection, particularly HPV16 and HPV18, is a significant cause of various cancers, including anogenital and oropharyngeal cancers.
• Developing safe and effective therapeutic vaccines against HPV-associated malignancies is a critical unmet medical need.

Purpose of the Study:

• To evaluate the immunogenicity and therapeutic efficacy of a recombinant fusion protein vaccine targeting CD40 and HPV16.E6/7 antigens (αCD40-HPV16.E6/7).
• To assess the vaccine's ability to elicit HPV16.E6/7-specific T-cell responses and anti-tumor immunity.

Main Methods:

• Development of a recombinant fusion protein (αCD40-HPV16.E6/7) combining a humanized anti-CD40 antibody with HPV16.E6/7 antigens.
• In vitro assessment of T-cell responses in head-and-neck cancer patients.
• In vivo studies in human CD40 transgenic (hCD40Tg) mice, evaluating T-cell priming with αCD40-HPV16.E6/7, poly(I:C), and montanide, and assessing therapeutic immunity against TC-1 tumors.

Main Results:

• The αCD40-HPV16.E6/7 vaccine evoked HPV16.E6/7-specific CD8+ and CD4+ T-cell responses in vitro and in hCD40Tg mice.
• Combination therapy with αCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16.E6/7-specific T cells, particularly CD8+ T cells, in mice.
• This combination demonstrated preventative and therapeutic immunity against tumors, significantly increasing HPV16-specific CD8+ cytotoxic T lymphocytes (CTLs) within tumors, correlating with reduced tumor volume.

Conclusions:

• CD40-targeting vaccines represent a highly immunogenic platform for HPV-associated malignancies, showing strong potential for clinical benefit.
• The findings support the development of CD40-targeting vaccines for HPV-associated cancers and potentially other cancer types in the future.