Expansion of human γδ T cells for adoptive immunotherapy using a bisphosphonate prodrug
| Autor: | Mohanad H. Nada, Asuka Kumagai, Craig T. Morita, Haruki Okamura, Yoshimasa Tanaka, Masashi Iwasaki, Kosuke Hayashi, Tomoharu Sugie, Nagahiro Minato, Masakazu Toi, Hirohito Kobayashi, Hong Wang, Hiroshi Kamitakahara, Kenji Matsumoto, Kaoru Murata-Hirai |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cancer Research Adoptive cell transfer bisphosphonate medicine.medical_treatment T cell T-Lymphocytes Cell Breast Neoplasms Major histocompatibility complex Immunotherapy Adoptive adoptive cancer immunotherapy 03 medical and health sciences zoledronic acid Mice Basic and Clinical Immunology Cancer immunotherapy medicine Animals Humans Prodrugs IL-2 receptor biology Vγ2Vδ2 T cells Diphosphonates Chemistry T-cell receptor Prostatic Neoplasms Receptors Antigen T-Cell gamma-delta General Medicine Original Articles Xenograft Model Antitumor Assays 3. Good health 030104 developmental biology medicine.anatomical_structure Treatment Outcome Oncology Cancer research biology.protein Tumor necrosis factor alpha Original Article Female farnesyl diphosphate synthase |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in a major histocombatibility complex (MHC) -unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA). PTA stimulated the expansion of Vγ2Vδ2 cells to purities up to 99%. These levels were consistently higher than those observed after expansion with zoledronic acid, the most commonly used stimulator for clinical trials. Cell numbers also averaged more than those obtained with zoledronic acid and the expanded Vγ2Vδ2 cells exhibited high cytotoxicity against tumor cells. The high purity of Vγ2Vδ2 cells expanded by PTA increased engraftment success in immunodeficient NOG mice. Even low levels of contaminating αβ T cells resulted in some mice with circulating human αβ T cells rather than Vγ2Vδ2 cells. Vγ2Vδ2 cells from engrafted NOG mice upregulated CD25 and secreted tumor necrosis factor-α and interferon-γ in response to PTA-treated tumor cells. Thus, PTA expands Vγ2Vδ2 T cells to higher purity than zoledronic acid. The high purities allow the successful engraftment of immunodeficient mice without further purification and may speed up the development of allogeneic Vγ2Vδ2 T cell therapies derived from HLA-matched normal donors for patients with poor autologous Vγ2Vδ2 T cell responses. |
| Databáze: | OpenAIRE |
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