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
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.
KeywordsCervical Cancer Recombinant Vaccinia Virus Tumour Antigen Peptide Loaded Dendritic Cell Peptide Loaded Dendritic Cell
Unable to display preview. Download preview PDF.
- 3.Mayordomo JI, Zorina T, Storkus WJ, Zitvogel L, Celluzzi C, Falo LD, Melief CJ, Ildstad ST, Kast WM, Deleo AB, (1995). Bone marrow derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic anti-tumour immunity. Nature Medicine 1 (12): 1297–1302PubMedCrossRefGoogle Scholar
- 4.Dsis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Lydon N, McGlynn E, Moe R, Cheever MA, (1994). Existent T cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54: 16–22Google Scholar
- 7.Borysiewicz LK,Fiander A,Nimako, Man S,Wilkinson GWG, Westmoreland D, Evans AS, Adams M,Stacey SN, Boursnell MEG, Rutherford E, Hickling JK, Inglis SC. (1996) A recombinant vaccinia virus encoding human papillomavirus types 16 and 18,E6 and E7 proteins as immunotherapy for cervical cancer. Lancet 347: 1523–27.CrossRefGoogle Scholar
- 8.Grabbe S,Beissert,Schwartz and Granstein RD (1995) Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy? Immunology Today 16(3)117–121.Google Scholar
- 9.Gabrilovich DI Nadaf S,Corak J,Berzofsky JA and Carbonne DP (1996). Dendritic cells in anti-tumour immune responses 11 Dendritic cells grown from bone marrow precursors but not mature DC from tumour bearing mice are effective antigen carriers in the therapy of established tumours. Cellular Immunology 170. 111–119.Google Scholar