In vivoantitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulationin vitro
| Autor: | Toru Miyake, Tomoyuki Ueki, Naomi Kitamura, Ngoc Pham Minh, Hirokazu Kodama, Satoshi Murata, Masatsugu Kojima, Katsushi Takebayashi, Eiji Mekata, Masaji Tani |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Adoptive cell transfer biology Effector Chemistry medicine.medical_treatment Immunotherapy Major histocompatibility complex Tumor antigen 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology Cancer immunotherapy In vivo 030220 oncology & carcinogenesis medicine biology.protein Cancer research CD8 |
| Zdroj: | International Journal of Cancer. 142:2335-2343 |
| ISSN: | 0020-7136 |
| Popis: | Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo. |
| Databáze: | OpenAIRE |
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