Generation of in Vitro Autologous Human Cytotoxic T-Cell Response to E7 and HER-2/Neu Oncogene Products Using Ex-Vivo Peptide Loaded Dendritic Cells

Abstract

Cytotoxic T-cells (CTL) have been shown to be capable of causing tumour-specific cell lysis when primed with tumour-specific antigenic peptides presented in conjunction with haplotype matched cell surface MHC class I molecules. For this approach to be successful for immunotherapy of tumours in vivo, it is essential that it is shown to be capable of generating adequate numbers of tumour-specific CTL either in vivo for active immunisation, or ex vivo for adoptive transfer therapy. A powerful means for ex vivo expansion of CTL has been recently shown to be antigen loaded autologous dendritic cells (DC)¹. It has also become possible to generate large numbers of these cells from bone marrow or blood derived precursor cells cultured in the presence of GM-CSF and 1L4². Furthermore, murine studies have confirmed the efficacy of these cells to evoke significant ex vivo and in vivo responses against tumour specific antigenic peptides, in particular, HPV 16 E7 and HER-2/neu oncogene products³, thereby creating the possibility of using these antigenic targets⁴ for effective immunotherapy of gynaecological cancers such as cervical and ovarian carcinomas in which these tumour associated antigens are expressed with 93%⁵ and 30%⁶ frequency, respectively.