Potential use of lymph node-derived HPV-specific T cells for adoptive cell therapy of cervical cancer.

Autor: van Poelgeest MI; Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands., Visconti VV; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands.; Department of Microbiology Diagnostic, University of Rome 'La Sapienza', Rome, Italy., Aghai Z; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., van Ham VJ; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., Heusinkveld M; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands.; Department of Medical Microbiology, Free University Medical Center, Amsterdam, The Netherlands., Zandvliet ML; Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Valentijn AR; Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands., Goedemans R; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., van der Minne CE; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., Verdegaal EM; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., Trimbos JB; Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands., van der Burg SH; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands., Welters MJ; Department of Medical Oncology, Leiden University Medical Center, Building 1, K1-P, PO box 9600, 2300 RC, Leiden, The Netherlands. m.j.p.schoenmaekers-welters@lumc.nl.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2016 Dec; Vol. 65 (12), pp. 1451-1463. Date of Electronic Publication: 2016 Sep 12.
DOI: 10.1007/s00262-016-1892-8
Abstrakt: Adoptive transfer of tumor-specific T cells, expanded from tumor-infiltrating lymphocytes or from peripheral blood, is a promising immunotherapeutic approach for the treatment of cancer. Here, we studied whether the tumor-draining lymph nodes (TDLN) of patients with human papillomavirus (HPV)-induced cervical cancer can be used as a source for ACT. The objectives were to isolate lymph node mononuclear cells (LNMC) from TDLN and optimally expand HPV-specific CD4+ and CD8+ T cells under clinical grade conditions. TDLN were isolated from 11 patients with early-stage cervical cancer during radical surgery. Isolated lymphocytes were expanded in the presence of HPV16 E6 and E7 clinical grade synthetic long peptides and IL-2 for 22 days and then analyzed for HPV16 specificity by proliferation assay, multiparameter flow cytometry and cytokine analysis as well as for CD25 and FoxP3 expression. Stimulation of LNMC resulted in expansion of polyclonal HPV-specific T cells in all patients. On average a 36-fold expansion of a CD4+ and/or CD8+ HPV16-specific T cell population was observed, which maintained its capacity for secondary expansion. The T helper type 1 cytokine IFNγ was produced in all cell cultures and in some cases also the Th2 cytokines IL-10 and IL-5. The procedure was highly reproducible, as evidenced by complete repeats of the stimulation procedures under research and under full good manufacturing practice conditions. In conclusion, TDLN represent a rich source of polyclonal HPV16 E6- and E7-specific T cells, which can be expanded under clinical grade conditions for adoptive immunotherapy in patients with cervical cancer.
Competing Interests: The authors declare that they have no conflict of interest.
Databáze: MEDLINE
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