期刊
CYTOTHERAPY
卷 15, 期 5, 页码 620-626出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2012.12.006
关键词
anti-CD3 mAb; chimeric antigen receptor; clinical trial; human T lymphocytes; RetroNectin; retroviral vectors; stability
类别
资金
- Dutch Cancer Foundation [DDHK99-1865, EMCR 2011-5159]
- European Commission [QLK3-1999-01262]
- European community [018914]
- Cancer Research Institute, New York, NY, USA
Background aims. The generation of gene-modified T cells for clinical adoptive T-cell therapy is challenged by the potential instability and concomitant high financial costs of critical T-cell activation and transduction components. As part of a clinical trial to treat patients with metastatic renal cell cancer with autologous T cells engineered with a chimeric antigen receptor (CAR) recognizing carboxy-anhydrase-IX (cArx), we evaluated functional stability of the retroviral vector, T-cell activation agent Orthoclone OKT3 (Janssen-Cilag, Beerse, Belgium) monoclonal antibody (mAb) and the transduction promoting agent RetroNectin (Takara, Otsu, Japan). Methods. Carboxy-anhydrase-IX chimeric antigen receptor retrovirus-containing culture supernatants (RTVsups) were generated from two packaging cell lines, Phoenix-Ampho (BioReliance, Sterling, UK) and PG13, and stored at -80 degrees C over 10 years and 14 years. For Orthoclone OKT3 and RetroNectin, aliquots for single use were prepared and stored at -80 degrees C. Transduction efficiencies of both batches of RTVsups were analyzed using the same lots of cryopreserved donor peripheral blood mononuclear cells, Orthoclone OKT3 and RetroNectin over time. Results. We revisit here an earlier report on the long-term functional stability of the RTVsup, observed to be 9 years, and demonstrate that this stability is at least 14 years. Also, we now demonstrate that Orthoclone OKT3 and RetroNectin are functionally stable for periods of at least 6 years and 10 years. Conclusions. High-cost critical components for adoptive T-cell therapy can be preserved for >= 10 years when prepared in aliquots for single use and stored at -80 degrees C. These findings may significantly facilitate, and decrease the financial risks of, clinical application of gene-modified T cells in multicenter studies.
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