Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

  • Authors:
    • Huiying Yu
    • Wei Chen
    • Changling Li
    • Di Lin
    • Junde Liu
    • Zien Yang
    • Jingang Yang
    • Yinghui Sun
    • Dongchu Ma
  • View Affiliations

  • Published online on: September 29, 2017     https://doi.org/10.3892/etm.2017.5228
  • Pages:5678-5686
0

Abstract

Cell‑based adoptive immunotherapy for the treatment of various cancer types has attracted the attention of scientists. However, due to the absence of unitary standard protocols to produce large quantities of clinical‑grade effector cells, it remains challenging to translate the experimental findings into clinical applications. The present study used methods complying with good manufacturing practice to induce effector cells from human peripheral blood mononuclear cells (PBMCs) of healthy donors by interleukin‑2 and anti‑Her‑2 antibody with or without anti‑CD3 antibodies (OKT3). The results indicated that the addition of OKT3 resulted in a greater expansion of the total cells and CD8+ T cells, and primarily induced the PBMCs to differentiate into CD3+ T cells. Regardless of the presence of OKT3, the expression of activating receptor of natural killer (NK) group 2, member D, and the inhibitory receptors of CD158a and CD158b on NK cells and NKT cells was increased, while the expression of NKp46 was inhibited on NK cells, but not on NKT cells. Furthermore, OKT3 did not affect the toxicity of the effector cells. Subgroup analysis indicated that although a variation of the composition of effector cells was present in different individuals under identical culture conditions, consistent marker expression on effector cells and target cell‑killing effects were observed in different subgroups treated with or without OKT3. Furthermore, western blot analysis indicated that OKT3, apart from its involvement in cell cycle regulation, affects transcription and protein translation during processes of proliferation and differentiation. The present study provided experimental data regarding the production of effector cells for adoptive immunotherapy as a clinical application.

Related Articles

Journal Cover

December 2017
Volume 14 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Yu, H., Chen, W., Li, C., Lin, D., Liu, J., Yang, Z. ... Ma, D. (2017). Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy. Experimental and Therapeutic Medicine, 14, 5678-5686. https://doi.org/10.3892/etm.2017.5228
MLA
Yu, H., Chen, W., Li, C., Lin, D., Liu, J., Yang, Z., Yang, J., Sun, Y., Ma, D."Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy". Experimental and Therapeutic Medicine 14.6 (2017): 5678-5686.
Chicago
Yu, H., Chen, W., Li, C., Lin, D., Liu, J., Yang, Z., Yang, J., Sun, Y., Ma, D."Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy". Experimental and Therapeutic Medicine 14, no. 6 (2017): 5678-5686. https://doi.org/10.3892/etm.2017.5228