Pediatric Hematology, Oncology and Stem Cell Transplantation, University Children's Hospital, Josef-Schneider-Strasse 2, Würzburg, Germany.
Cancer Immunol Immunother. 2011 Feb;60(2):173-86. doi: 10.1007/s00262-010-0928-8. Epub 2010 Oct 24.
T cell-mediated immunotherapy against malignancies has been shown to be effective for certain types of cancer. However, ex vivo expansion of tumor-reactive T cells has been hindered by the low precursor frequency of such cells, often requiring multiple rounds of stimulation, resulting in full differentiation, loss of homing receptors and potential exhaustion of the expanded T cells. Here, we show that when using highly purified naïve CD8+ T cells, a single stimulation with peptide-pulsed, IFNγ/LPS-matured dendritic cells in combination with the sequential use of IL-21, IL-7 and IL-15 is sufficient for extensive expansion of antigen-specific T cells. Short-term expanded T cells were tumor-reactive, multifunctional and retained a central-memory-like phenotype (CD62L+, CCR7+, CD28+). The procedure is highly reproducible and robust as demonstrated for different healthy donors and for cancer patients. Such short-term tumor-antigen-primed, multifunctional T cells may therefore serve as a platform to target different malignancies accessible to immunotherapy.
T 细胞介导的免疫疗法已被证明对某些类型的癌症有效。然而，肿瘤反应性 T 细胞的体外扩增受到这些细胞的低前体频率的阻碍，通常需要多次刺激，导致完全分化、归巢受体丧失和扩增的 T 细胞潜在衰竭。在这里，我们表明，当使用高度纯化的幼稚 CD8+T 细胞时，用肽脉冲刺激、IFNγ/LPS 成熟的树突状细胞进行单次刺激，结合 IL-21、IL-7 和 IL-15 的顺序使用，足以广泛扩增抗原特异性 T 细胞。短期扩增的 T 细胞具有肿瘤反应性、多功能性，并保留中央记忆样表型（CD62L+、CCR7+、CD28+）。该程序具有高度的可重复性和稳健性，已在不同的健康供体和癌症患者中得到证明。因此，这种短期肿瘤抗原引发的、多功能的 T 细胞可以作为针对免疫疗法可及的不同恶性肿瘤的平台。
