Adoptive Transfer of Invariant NKT Cells as Immunotherapy for Advanced Melanoma: A Phase I Clinical Trial
| Autor: | Mark A. Exley, Anita Giobbie-Hurder, Steven P. Balk, Yo Mizukami, Tetsuro Sasada, Jerome Ritz, Lianne E.M. Vriend, Kenneth LeClair, F. Stephen Hodi, Heather Daley, Glenn Dranoff, Christine Canning, Phillip Friedlander, Wanyong Zeng, David M. Nemer, Nadia Alatrakchi, Simon Yue, Justice Clark |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Adoptive cell transfer business.industry medicine.medical_treatment Leukapheresis Immunotherapy Natural killer T cell Peripheral blood mononuclear cell 03 medical and health sciences Interleukin 10 030104 developmental biology Immune system Oncology Immunology Medicine business Interleukin 4 |
| Zdroj: | Clinical Cancer Research. 23:3510-3519 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-16-0600 |
| Popis: | Purpose: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown clinical responses. Therefore, a phase I clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB–IV melanoma. Experimental Design: Residual iNKT cells [ Results: Expanded iNKT cells produced IFNγ, but limited or undetectable IL4 or IL10. Three iNKT infusions each were completed on 9 patients, and produced only grade 1–2 toxicities. The 4th patient onward received systemic GM-CSF with their second and third infusions. Increased numbers of iNKT cells were seen in PBMCs after some infusions, particularly when GM-CSF was also given. IFNγ responses to α-galactosylceramide were increased in PBMCs from some patients after infusions, and delayed-type hypersensitivity responses to Candida increased in 5 of 8 evaluated patients. Three patients have died, three were progression-free at 53, 60, and 65 months, three received further treatment and were alive at 61, 81, and 85 months. There was no clear correlation between outcome and immune parameters. Conclusions: Autologous in vitro expanded iNKT cells are a feasible and safe therapy, producing Th1-like responses with antitumor potential. Clin Cancer Res; 23(14); 3510–9. ©2017 AACR. |
| Databáze: | OpenAIRE |
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