HPV DNA Test and Experimental DNA Vaccine

The National Cancer Institute states that “virtually all” cervical cancers are caused by HPV infection.  The association is so strong that the FDA recently approved a DNA test for HPV that many believe could supplant PAP smear.  This is great news for patients who do not have cervical cancer, yet.  But what if you do?… HPV infection introduces two oncoproteins, HPV E6 and HPV E7) into the genome of infected cells that deregulate many cellular pathways resulting in the cancer phenotype.  HPV E6 binds p53, tagging it for destruction by ubiquitylation and degradation in proteasomes., thereby blocking p53-mediated apoptosis of transformed cells.  HVP E7 binds the pRb and renders it inactive, thereby removing control from the E2F transcription factors that govern the cell cycle, leading to uncontrolled proliferation.  HPV E6 also induces hTERT (temolerase) expression, thereby immortalizing transformed cells.  (See diagram from OncoHealth.) image_hpv

Inovio Pharmaceuticals initiated a clinical trial of its DNA vaccine against HPV.  Importantly, In a phase I trial of VGX-3100, Inovio demonstrated that this HPV immunotherapy produced high levels of durable T cell immune responses, notably CD8+ T cells, in 78% of all patients. These CD8+ T cells showed the functional ability to kill target cells displaying the antigens E6 and E7. In preclinical animal models, this DNA-based immunotherapy demonstrated 100% protection against HPV E6 and E7-expressing tumors and prevented or delayed the growth of such tumors. The vaccine is delivered with a gene encoding IL-12, which promotes the development T-helper cells, which are required for a robust cellular and humoral immune responses.

Of course, Gardasil, a quadrivalent PREVENTATIVE vaccine for HPV 6, 11, 16, and 18, is approved to immunize patients against HPV infctions.  Seventy percent of cervical cancers are caused by HPV 16 and 18; 90% of genital warts are caused by HPV 6 and 11.  Gardasil had sales of $2.1B in 2013.  Vaccines against HPV E6 and E7 for cervical cancer treatment are not designed to prevent HPV infection.

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