Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.14.5909

Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer - a Feasibility Study  

Ramanathan, Priya (Department of Molecular Oncology, Cancer Institute (WIA))
Ganeshrajah, Selvaluxmy (Department of Radiation Oncology, Cancer Institute (WIA))
Raghanvan, Rajalekshmi Kamalalayam (Department of Oncopathology, Cancer Institute (WIA))
Singh, Shirley Sundar (Department of Oncopathology, Cancer Institute (WIA))
Thangarajan, Rajkumar (Department of Molecular Oncology, Cancer Institute (WIA))
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.14, 2014 , pp. 5909-5916 More about this Journal
Abstract
Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms - saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.
Keywords
Dendritic cells; immunotherapy; cancer vaccines; cervical cancer; HPV;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Alberts DS, Kronmal R, Baker LH, et al (1987). Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study. J Clin Oncol, 5, 1791-5.
2 Ardon H, Van Gool SW, Verschuere T, et al (2012). Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: Results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother, 61, 2033-44.   DOI
3 Banchereau J, Steinman RM (1998). Dendritic cells and the control of immunity. Nature, 392, 245-52.   DOI   ScienceOn
4 Cadron I, Jakobsen A, Vergote I (2005). Report of an early stopped randomized trial comparing cisplatin vs. cisplatin/ ifosfamide/ 5-fluorouracil in recurrent cervical cancer. Gynecol Obstet Invest, 59, 126-9.
5 Claesson MH (2009). Why current peptide-based cancer vaccines fail: lessons from the three Es. Immunother, 1, 513-6.
6 Cromme FV, van Bommel PF, Walboomers, et al (1994). Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumors. Br J Cancer, 69, 1176-81.   DOI   ScienceOn
7 Curti A, Tosi P, Comoli P, Terragna C, et al (2007). Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumor idiotype protein or idiotype (VDJ)-derived class I-restricted peptides. Br J Haematol, 139, 415-24.   DOI
8 Das D, Rai AK, Kataki AC, et al (2012). Nested multiplex PCR based detection of HPV in cervical carcinoma patients of North-East India. Asian Pac J Cancer Prev, 13, 785-90   DOI
9 de Jong A, van Poelgeest MI, van der Hulst JM, et al (2004). Human papillomavirus type 16-positive cervical cancer is associated with impaired CD4+ T-cell immunity against early antigens E2 and E6. Cancer Res, 64, 5449-55.   DOI   ScienceOn
10 De Vries IJ, Lesterhuis WJ, Scharenborg NM, et al (2003). Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res, 9, 5091-100
11 Dohnal AM, Witt V, Hugel H, Holter W, Gadner H, Felzmann T (2007). Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy, 9, 755-70.   DOI
12 Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.   DOI   ScienceOn
13 Hsu FJ, Benike C, Fagnoni F et al (1996). Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med, 2, 52-8   DOI   ScienceOn
14 Morse MA, Coleman RE, Akabani G, et al (1999). Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res, 59, 56-8.
15 Intradermal delivery of vaccines: a review of the literature and potential for development or use in low and middle-income countries. Seattle: Program for Appropriate Technology In Health (PATH) (2009).
16 Liau LM, Prins RM, Kiertscher SM, et al (2005). Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res, 11, 5515-25.   DOI   ScienceOn
17 Marchand M, Weynants P, Rankin E, et al (1995). Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3. Int J Cancer, 63, 883-5.   DOI
18 Nagorsen D, Scheibenbogen C, Schaller G, et al (2003). Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients. Int J Cancer, 105, 221-5.   DOI
19 Okoshita C, Takikawa M, Kume A, et al (2012). Dendritic cellbased vaccination in metastatic melanoma patients: phase II clinical trial. Oncol Rep, 28, 1131-8.
20 Pandey S, Mishra M, Chandrawati (2012). Human papilloma virus screening in North Indian Women. Asian Pac J Cancer Prev, 13, 2643-46   DOI   ScienceOn
21 Scatchard K, Forrest JL, Flubacher M, Cornes P, Williams C, (2012). Chemotherapy for metastatic and recurrent cervical cancer. Cochrane Database Syst Rev, 10, 6469.
22 Srivani R, Nagarajan B, (2003). A prognostic insight on in vivo expression of interleukin-6 in uterine cervical cancer. Int J Gynecol Cancer, 13, 331-9.   DOI
23 Wheeler CJ, Das A, Liu G, Yu JS, Black KL (2004). Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res, 10, 5316-26.   DOI
24 Tartour E, Gey A, Sastre-Garau X, et al (1998). Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas. J Natl Cancer Inst, 90, 287-94.   DOI
25 Thumann P, Moc I, Humrich J, et al (2003). Antigen loading of dendritic cells with whole tumor cell preparations. J Immunol Methods. 277, 1-16.   DOI
26 Tindle RW (2002). Immune evasion in human papillomavirusassociated cervical cancer. Nat Rev Cancer, 2, 59-65.   DOI
27 Wu XM, Liu X, Jiao Q-F, et al (2014). Cytotoxic T lymphocytes elicited by dendritic cell-targeted delivery of human papillomavirus type-16 E6/E7 fusion gene exert lethal effects on CaSki Cells. Asian Pac J Cancer Prev, 14, 2447-51.   과학기술학회마을   DOI
28 Yu JS, Wheeler CJ, Zeltzer PM, et al (2001). Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res, 61, 842-47.
29 Reinhard G, Marten A, Kiske SM, et al (2002). Generation of dendritic cell-based vaccines for cancer therapy. Br J Cancer, 86, 1529-33.   DOI