Immunotherapy of human cervical high-grade cervical intraepithelial neoplasia with microparticle-delivered human papillomavirus 16 E7 plasmid DNA

Vaccine Strategies against Human Papillomavirus: A Discussion Focused on Developing Countries

“…One is the ZYC-101a vaccine (MGI Pharma, MA, USA), which encodes multiple E6 and E7 epitopes (for activation of cytotoxic T lymphocytes -CTLs) of HPV-16 and -18. This vaccine was tested through the administration of three intramuscular doses and the results showed that significantly more types of CIN-2/3 lesions were successfully treated in young women (under 25) than in those who received placebo doses [79,80]. Another example of DNA vaccine, called Sig/E7detox/HSP70, was administered in Phase I clinical trials.…”

Plant Production of Vaccine Against HPV: A New Perspectives

“…There are many different types of therapeutic vaccine candidates based on viral gene peptides and proteins (Xie et al, 2011;Kenter et al, 2008;Melief et al, 2007;Fiander et al, 2006), DNA (Alvarez-Salas et al;, Sheets et al, 2003 and various viral and bacterial vectors (Brandsma et al, 2009, Davison et al, 2003. They all aim to induce specific cellmediated immunity and in most cases the targets are the E6 and E7 proteins.…”

Hepatitis B Surface Antigen-based Vaccines for Human Neoplastic Disease

“…CTL responses have also been defined from E4 and L1 proteins (Steele et al, 2002). Human clinical trials targeting HPV-associated antigens have resulted in poor cellular immune responses (Borysiewicz et al, 1996;Ressing et al, 1996;van Driel et al, 1999;Muderspach et al, 2000;Kaufmann et al, 2002;Sheets et al, 2003), possibly related to the immunosuppressive effects mediated by E7 and E6 proteins, from the vaccine recipients' tumours.…”

“…However preliminary studies using E6-and E7-targeting vaccines in humans has met with limited success (Borysiewicz et al, 1996;van Driel et al, 1999;Muderspach et al, 2000;Davidson et al, 2003;Frazer et al, 2004;Hallez et al, 2004;Kenter et al, 2008;Trimble et al, 2009) and there is currently no immunotherapeutic approach to treat HPV-associated carcinoma. Clinical trials in humans have not been able to demonstrate successful elimination of disease from vaccine recipients (Borysiewicz et al, 1996;Ressing et al, 1996;van Driel et al, 1999;Muderspach et al, 2000;Kaufmann et al, 2002;Baldwin et al, 2003;Sheets et al, 2003). E6 and E7 are of low immunogenicity in natural infection as they are specifically expressed in keratinocytes, which do not express costimulatory molecules (Bal et al, 1990;Doan et al, 1998;Azoury-Ziadeh et al, 2001) and in combination with other immune evasive mechanisms of HPV (reviewed in Tindle, 2002), the host's immune system may become tolerised to these oncoproteins (Barnard et al, 2000).…”

“…To date, human vaccine clinical trials directed towards HPV-associated E6 and E7 antigens have resulted in poor cellular immune responses and limited clinical improvement (Borysiewicz et al, 1996;Ressing et al, 1996;van Driel et al, 1999;Muderspach et al, 2000;Kaufmann et al, 2002;Sheets et al, 2003;Hallez et al, 2004;Kenter et al, 2008;Trimble et al, 2009 …”