Roberto Montes de Oca Luna, Ph.D.

Research

Cervical cancer remains a leading cause of cancer-related mortality in women, particularly in developing countries. The causal association between genital human papillomavirus (HPV) infection and cervical cancer has been firmly established and the oncogenic potential of certain HPV types has been clearly demonstrated. Vaccines targeting the oncogenic proteins E6 and E7 of HPV-16 and 18 are the focus of current vaccines development. Calreticulin (CRT), an abundant 46 kDa Ca2+-binding protein located in the endoplasmic reticulum (ER), has been shown to associate with peptides delivered into the ER by transporters associated with antigen processing (TAP-1 and TAP-2) and with MHC class 1-132 microglobulin molecules to aid in antigen presentation. Previous studies have shown that exogenous administration of CRT complexed with peptides in vitro can elicit a peptide-specific CD8+ T cell response. In this study a replication-deficient adenovirus expressing CRT/E7 (Ad-CRE/E7) was constructed to enhance the immunological efficiency ofHPV-16 E7 antigen against TC-1 tumor, an animal model of cervical cancer. Cells infected with the Ad-CRT/E7 were shown to produce and address the protein CRT-E7 to the endoplasmic reticulum.The antitumor effect induced by administration of Ad-CRT/E7 was compared against an adenovirus expressing E7. Measurements of tumor size indicate that indeed calreticulin-E7 plays a significant role to protect mice against tumor development than that which resulted from E7 alone. Requested.