Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit.

Autor: Nickles E; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Life Sciences Institute, Immunology Programme, National University of Singapore, Singapore, Singapore.; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Dharmadhikari B; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Life Sciences Institute, Immunology Programme, National University of Singapore, Singapore, Singapore.; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Yating L; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Life Sciences Institute, Immunology Programme, National University of Singapore, Singapore, Singapore.; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Walsh RJ; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Koh LP; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Poon M; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Tan LK; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Wang LZ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Ang Y; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Asokumaran Y; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Chong WQ; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Huang Y; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Loh KS; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Tay J, Soo R; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore., Koh M; Health Sciences Authority, Singapore, Singapore., Ho LP; Health Sciences Authority, Singapore, Singapore., Chan M; Health Sciences Authority, Singapore, Singapore., Niam M; Health Sciences Authority, Singapore, Singapore., Soh M; Health Sciences Authority, Singapore, Singapore., Luah YH; Health Sciences Authority, Singapore, Singapore., Lim CM; Department of Otolaryngology - Head and Neck Surgery, Singapore General Hospital, Singapore, Singapore., Kaliaperumal N; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Au VB; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Talib NBSN; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Sng R; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Connolly JE; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Goh BC; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, Singapore. phcgbc@nus.edu.sg., Schwarz H; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. phssh@nus.edu.sg.; Life Sciences Institute, Immunology Programme, National University of Singapore, Singapore, Singapore. phssh@nus.edu.sg.; Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. phssh@nus.edu.sg.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2022 Jun; Vol. 71 (6), pp. 1531-1543. Date of Electronic Publication: 2021 Oct 18.
DOI: 10.1007/s00262-021-03075-3
Abstrakt: Introduction: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells.
Methods: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX).
Results: Of the 12 patients treated, 9 received full 7 vaccine doses with a mean administered cell count of 23.9 × 10 6 per dose. Treatment was well tolerated with only 4 cases of grade 1 related adverse events. A partial response was obtained in 1 patient, and 4 patients are still benefitting from a progression free survival (PFS) of currently 2-3 years. The mean pre-treatment neutrophil: lymphocyte ratio was 3.4 and a value of less than 3 was associated with prolonged median PFS. Progressors were characterized by a high frequency of naïve T cells but a low frequency of CD8 + effector T cells while patients with a clinical benefit (CB) had a high frequency of memory T cells. Patients with CB had lower plasma EBV DNA levels, and a reduction after vaccination.
Conclusion: CD137L-DC-EBV-VAX was well tolerated. The use of CD137L-DC-EBV-VAX is demonstrated to be safe. Consistent results were obtained from all 12 patients, indicating that CD137L-DC-EBV-VAX induces an anti-EBV and anti-NPC immune response, and warranting further studies in patients post effective chemotherapy.
Precis: The first clinical testing of CD137L-DC, a new type of monocyte-derived DC, finds that CD137L-DC are safe, and that they can induce an immune response against Epstein-Barr virus-associated nasopharyngeal carcinoma that leads to tumor regression or prevents tumor progression.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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