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Optimization of lymphapheresis for manufacturing autologous CAR-T cells

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Abstract

Collection of CD3+ lymphocytes via lymphapheresis is essential for manufacturing autologous chimeric antigen receptor (CAR) T cells. Optimization of timing and procedures for lymphapheresis for each patient is critical because patients often have progressive diseases and receive medications that could reduce T cell counts. We conducted a retrospective study of clinical data from 28 patients who underwent lymphapheresis for CD19-directed CAR-T therapy with tisagenlecleucel to identify factors that could affect CD3+ lymphocyte yields. The numbers of CD3+ cells in peripheral blood were significantly correlated with CD3+ cell yields (correlation coefficient r = 0.84), which enabled us to estimate the volume of blood to process before apheresis. We also found that small cell ratio (SCR) at the apheresis site precisely reflected the proportion of lymphocytes, especially in patients without circulating blasts (coefficient of determination: r2 = 0.9). We were able to predict the CD3+ cell yield and prevent excessive apheresis by measuring pre-apheresis circulating CD3+ cell counts and monitoring SCR. Collectively, these results will help us to establish a strategy for optimization of lymphapheresis procedures for CAR-T cell production on a patient-by-patient basis.

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Acknowledgements

We acknowledge the technical staffs at Center for Cellular and Molecular Medicine, Kyushu University Hospital for flow cytometric analysis and the clinical engineering technologists at Department of Medical Technology, Kyushu University Hospital for assistance with procedure of apheresis. We also thank the apheresis nurses at Blood Transfusion Center, Kyushu University Hospital for clinical care contributions.

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Authors and Affiliations

  1. Center for Cellular and Molecular Medicine, Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Ikumi Yamanaka, Takuji Yamauchi, Tomoko Henzan, Teppei Sakoda, Kyoko Miyamoto, Takahiro Maeda & Yuya Kunisaki

  2. Department of Medical Technology, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Hiroyuki Mishima

  3. Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Hiroaki Ono, Yuhki Koga & Shouichi Ohga

  4. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Yasuhiro Nakashima & Yoshihiro Ogawa

  5. Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Koji Kato, Toshihiro Miyamoto & Koichi Akashi

  6. Molecular and Cell Processing Center, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Shinichi Mizuno

  7. Division of Precision Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Takahiro Maeda

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  1. Ikumi Yamanaka
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  2. Takuji Yamauchi
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Correspondence to Yuya Kunisaki.

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Yamanaka, I., Yamauchi, T., Henzan, T. et al. Optimization of lymphapheresis for manufacturing autologous CAR-T cells. Int J Hematol 114, 449–458 (2021). https://doi.org/10.1007/s12185-021-03191-x

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  • DOI: https://doi.org/10.1007/s12185-021-03191-x

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