Methods for improving the efficacy and expansion of immune cells
一种免疫细胞、免疫效应细胞的技术，应用在用于改善免疫细胞的功效和扩张领域，能够解决依赖抗体可获得性、抗体昂贵、成本增加等问题
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[0247] As used herein, the term "obtaining" means obtaining a physical entity (e.g., a sample, cell or population of cells, polypeptide, nucleic acid, or sequence) or value, such as a value, by "directly obtaining" or "indirectly obtaining" the physical entity or value. In one embodiment, obtaining involves obtaining or harvesting a cell or population of cells (eg, an immune effector cell or population as described herein). "Directly obtaining" means performing a process (eg, performing a synthetic method or an analytical method or a purification method) to obtain a physical entity or value. "Indirect acquisition" means receiving a physical entity or value from another party or source (eg, a third-party laboratory that directly acquires the physical entity or value). Direct access to physical entities includes performing methods involving physical changes of physical substances (eg, starting materials). Exemplary changes include creating a physical entity from two or more sta...
Embodiment 1
[1034] Example 1: Optimizing CART Production with Exogenous Cytokines
[1035] Cytokines have important functions related to T cell expansion, differentiation, survival and homeostasis. One of the most important cytokine families in clinical use is the common gamma chain (γc) family of cytokines, which includes interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL- 21 (Liao et al., 2013, Immunity, 38:13-25). IL-2 has been extensively studied as an immunotherapeutic agent for cancer. IL-2 supplementation in clinical trials enhanced the anti-tumor ability of anti-CD19 CAR-T cells (Xu et al., 2013, Lymphoma, 54:255-60). However, the administration of IL-2 is limited by side effects and the propensity of regulatory T cells to expand and the effect of activated induced cell death (AICD) (Malek et al., 2010, Immunity, 33:153-65; and Lenardo et al., 1999, Annu Rev Immunol, 17:221-53). IL-7, IL-15 and IL-21 can each enhance the effectiveness of adoptive immunotherapy and appear to ...
Embodiment 2
[1078] Example 2: Effect of CD25 depletion on cell growth and transduction efficiency
[1079] The interleukin-2a chain, also known as CD25, is expressed by regulatory T cells (Treg), but is also observed in chronic B-cell leukemia (CLL) cells (greater than 85% of CLL patients). Tregs have immunosuppressive functions and can prevent the efficacy of immunotherapy, for example by inhibiting T cell proliferation. Current isolation or enrichment of T cells from CLL patients by apheresis usually contains significantly increased ratios of Treg and CLL cells. Depletion of Treg and CLL cells in the starting material by a CD25 depletion method can significantly improve the purity of effector T cells, thereby increasing the potency of CAR19-expressing T cells (such as CART19 cells).
[1080] Optimizing CD25 Consumption
[1081] Validation experiments were performed using Miltenyi's CD25 reagent in the CliniMACS system to identify optimal conditions from CD25 depletion in apheresis of ...
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