Expert Opin Investig Drugs. 1999 Jun;8(6):761-76.
Vaccines for human papillomavirus-associated anogenital disease and cervical cancer: practical and theoretical approaches.
1Sir Albert Sakzewski Virus Research Centre, Royal Children’s Hospital, Herston Road, Herston, QLD, 4029, Australia.
The association of genital warts, cervical dysplasia and cervical cancer with certain human papillomavirus (HPV) types indicates that vaccine strategies that target the virus could be effective in controlling disease onset and progression. Three vaccine strategies are available. Firstly, a prophylactic approach of immunisation with HPV virus-like particles to elicit neutralising antibody would prevent infection. Secondly, vaccination targeting replicating virus in suprabasal cells of infected anogenital epithelium would be an effective therapy for infection and early dysplasias. Thirdly, immunotherapy directed to the oncoprotein products of the HPV E6 and E7 open reading frames would be effective in the control of cervical carcinoma. We examine how these strategies may be augmented by contemporary vaccine technologies, in particular through the use of live recombinant vaccine vectors, specific targeting of antigen processing pathways, dendritic cell and ‘polytope’ approaches, to produce ‘designer’ vaccines of maximum specificity and efficacy. How these approaches are being exploited by vaccine manufacturers and in clinical trials is discussed.
Anticancer Res. 2003 Sep-Oct;23(5b):4293-303.
Dendritic cell-based vaccines in breast and gynaecologic cancer.
1Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Major advances in understanding the functional interactions between tumour cells and the host immune system, in particular the generation and regulation of T cell immunity, have revived interest in cancer vaccination strategies. A crucial step for mounting an anti-tumour response is the capture, processing and presentation of tumour antigens (TA) to cognate T cells by professional antigen-presenting cells (APC), followed by their activation and clonal proliferation. Dendritic cells (DC) are potent APC with the unique ability to stimulate primary immune responses. Animal models have demonstrated that TA-charged DC can activate specific cytotoxic T cells (CTL) and even regression of established tumours in cancer-bearing hosts. These findings, as well as the elaboration of methods for generating large numbers of DC ex vivo, have provided a compelling rationale for using DC as potent adjuvants to deliver TA to the immune system in order to trigger or amplify an inadequate response. The capacity of TA-pulsed DC to induce significant CTL immunity translating into occasional therapeutic benefit has been documented in several clinical settings including B cell lymphoma, myeloma, melanoma, prostate, colon, ovarian and renal cell carcinoma. In this review, we summarize key biological functions of DC and focus on recent DC-based vaccination trials of breast, ovarian and cervical cancer.
Arch Gynecol Obstet. 2014 Jan;289(1):155-62. doi: 10.1007/s00404-013-2938-1. Epub 2013 Aug 3.
In vitro and in vivo evaluations of human papillomavirus type 16 (HPV16)-derived peptide-loaded dendritic cells(DCs) with a CpG oligodeoxynucleotide (CpG-ODN) adjuvant as tumor vaccines for immunotherapy of cervical cancer.
1Gynecology Department, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, China, firstname.lastname@example.org.
To evaluate the immunotherapeutic potentials for human dendritic cells (DCs) loaded with different HPV16-associated antigens, including HPV16E7 (E) protein, HPV16E7 polypeptide (P), as well as CpG-oligodeoxynucleotide (ODN) 2006 as a promising immune adjuvant for vaccination against cervical carcinoma.
DCs derived from human peripheral blood and cord blood were isolated and loaded with HPV-derived protein or peptides, in combination with CpG-ODN2006 as a potential adjuvant. The IL-12 level, the allogeneic T cell-stimulatory capacity and the cytotoxicity of cytotoxic T lymphocytes (CTLs) were evaluated in vitro. Furthermore, an immune reconstitution model of human cervical carcinoma in SCID mice was used to assess the anti-tumor effects in vivo. The tumor sizes, the expression of IgG and IFN-γ, and the presence of the human CD3(+), CD4(+) and CD8(+) T cells were measured in the mice inoculated with different DCs.
The antigen-loaded DCs displayed obvious anti-tumor activities in vitro and in vivo, and showed no toxicity to normal cells. The level of IL-12, an important cytokine for immune response, was up-regulated in all mice inoculated with antigen-loaded DCs. Stimulation and activity of CTLs were increased after treatment with antigen-loaded DCs. Significantly, DCs loaded with HPV16E7 polypeptide (P) showed the most distinguished immunotherapeutic activities, and such effect was further enhanced when HPV16E7 polypeptide (P) was used in combination with CpG-ODN2006. Interestingly, the same results were obtained in vivo: the tumor size was decreased, and IgG and IFN-γ levels were increased after the SCID mice were inoculated with the loaded DCs.
HPV16E7 polypeptide combined with the immune adjuvant CpG-ODN2006 could be a suitable HPV16-associated tumor antigen. The research provides a new strategy for generating DCs vaccines for immunotherapy of cervical cancer.
Keywords: Immunotherapy; Dendritic cells; HPV16E7 polypeptide; CpG-ODN2006