Optimization of lymphapheresis for manufacturing autologous CAR-T cells

Yamanaka, I; Yamauchi, Takuji; Henzan, Tomoko; Sakoda, Teppei; Miyamoto, Kyoko; Mishima, Hiroyuki; Ono, Hiroaki; Koga, Yuhki; Nakashima, Yukiko; Katô, Kôji; Miyamoto, Toshihiro; Mizuno, Shinichi; Ogawa, Yoshihiro; Ohga, Shouichi; Akashi, Koichi; Maeda, Takahiro; Kunisaki, Yuya

doi:10.1007/s12185-021-03191-x

Cited by 6 publications

(13 citation statements)

References 20 publications

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“…This direct relationship has been corroborated in studies with healthy donors [ 20 ]. More importantly, this correlation has also been proven in series of patients diagnosed with NHL, ALL, MM, CLL, and solid neoplasms [ 12 , 21 , 22 , 23 , 24 , 25 , 26 ]. While the power of the correlation between CD3+ lymphocyte count in peripheral blood and the final target cell yield was high (correlation coefficient r = 0.57–0.86) [ 21 , 25 , 26 ], there is no established minimum peripheral blood lymphocyte count before starting the collection of T cells [ 13 ].…”

Section: Factors Affecting Mononuclear Cell Yieldmentioning

confidence: 69%

“…More importantly, this correlation has also been proven in series of patients diagnosed with NHL, ALL, MM, CLL, and solid neoplasms [ 12 , 21 , 22 , 23 , 24 , 25 , 26 ]. While the power of the correlation between CD3+ lymphocyte count in peripheral blood and the final target cell yield was high (correlation coefficient r = 0.57–0.86) [ 21 , 25 , 26 ], there is no established minimum peripheral blood lymphocyte count before starting the collection of T cells [ 13 ]. Published series have described successful collections even with cell counts as low as 160–330 lymphocytes/µL [ 13 , 21 , 22 , 25 , 27 , 28 , 29 ].…”

Section: Factors Affecting Mononuclear Cell Yieldmentioning

confidence: 69%

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Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

Piñeyroa¹,

Cid²,

Lozano³

2022

Transfus Med Hemother

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Background: The major drug regulatory agencies have approved chimeric antigen receptor (CAR) T cells for the treatment of some B-cell lymphoproliferative diseases. Their use is expanding, and new indications will be approved. Efficient mononuclear cell collection by apheresis providing enough T cells is a critical step in further CAR T-cell manufacturing process. It is important that apheresis units are prepared for the collection of the required T cells for manufacturing with the highest efficiency and safety for the patient. Summary: Several series have studied different characteristics that could influence the collection efficiency of T cells for CAR T-cell manufacturing. Also, an effort has been made to identify predictors of the total number of target cells collected. Despite these publications and the large number of ongoing clinical trials, consensus protocols in apheresis are scarce. Key Messages: The aim of this review was to summarize the set of measures described to optimize apheresis and ensure patient safety. Moreover, we also propose, in a practical approach, a way to apply this knowledge to the daily routine in the apheresis unit.

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Section: Factors Affecting Mononuclear Cell Yieldmentioning

confidence: 69%

Section: Factors Affecting Mononuclear Cell Yieldmentioning

confidence: 69%

Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

Piñeyroa¹,

Cid²,

Lozano³

2022

Transfus Med Hemother

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“…Steady-state peripheral blood leukapheresis, or the collection of peripheral blood MNCs for extracorporeal photopheresis (ECP) have been used for therapeutic purposes in chronic GVHD [19][20][21][22]. Similarly, lymphapheresis is the first step of the manufacturing process of chimeric antigen receptor (CAR) T cells and has been a safe and reliable procedure for the collection of CD3 + lymphocytes from patients after allogeneic HCT [23,24]. These procedures require a sufficient number of cells for therapeutic processing which could be a major challenge in chronic GVHD where patients are often frail or lymphopenic.…”

Section: Discussionmentioning

confidence: 99%

Collection of peripheral blood mononucleated cells for chronic graft-versus-host disease immunology research: safety and effectiveness of leukapheresis in 132 patients

et al. 2022

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Background Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and non-relapse mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Its biology, however, remains poorly understood, making the studies of its biology and immunomodulatory therapies a difficult task. Such research is often hampered by lymphopenia which is common in these patients and precludes studies of critical cellular subsets across the spectrum of severity of disease. This study explores the potential of leukapheresis to safely acquire and efficiently store immune cells for immunology research in chronic GVHD. Methods This is a cross-sectional study in which 132 consecutively accrued patients undergo optional research leukapheresis and a one-week comprehensive outpatient evaluation. Baseline clinical and laboratory data and efficiency of the procedure were reported. Results Ninety-four of 132 patients (71%) achieved the goal collection of 2 × 10^9 PBMNCs with a mean volume processed of 4.6 L. Only mild decreases in hemoglobin, platelet, lymphocyte and monocytes were observed. All adverse events were mild (grade 1) and had resolved by the time of discharge from the apheresis unit. Conclusion This study demonstrates feasibility, safety, and efficiency of research leukapheresis in a frail patient population. Results presented promote leukapheresis as a standard research practice option in studies of chronic GVHD in humans which may expedite advances in our understanding of this complex multisystem disease.

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“…[13][14][15][16][17] In elderly adult patients diagnosed with lymphoma, only few detailed reports on T-cell collection for CAR T-cell therapy were published. 18,19 In this study, we provide comprehensive lymphapheresis results from elderly and pretreated lymphoma patients intended to undergo treatment with Tisagenlecleucel.…”

Section: Introductionmentioning

confidence: 99%

“…So far, thorough analyses of the lymphapheresis process in CAR T‐cell patients have been largely focused on pediatric patients 13–17 . In elderly adult patients diagnosed with lymphoma, only few detailed reports on T‐cell collection for CAR T‐cell therapy were published 18,19 . In this study, we provide comprehensive lymphapheresis results from elderly and pretreated lymphoma patients intended to undergo treatment with Tisagenlecleucel.…”

Section: Introductionmentioning

confidence: 99%

Apheresis for chimeric antigen receptor T‐cell production in adult lymphoma patients

et al. 2022

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Background To date, in‐depth analysis of leukapheresis products as starting material for CAR T‐cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients. Study Design and Methods Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109, a CD3‐positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product. Results Twenty‐three patients (age 37–77 years) and 24 apheresis runs were evaluated. The median CD3‐positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/μl (range: 70–1345 cells/μl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109–47.4 × 109). The median CD3‐positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109–6.915 × 109), which resulted in a median collection efficiency for CD3‐positive lymphocytes of 63.7% (range: 9.56%–93.6%). No adverse events associated with the apheresis process were observed. Conclusions Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3‐positive lymphocytes for CAR T‐cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre‐emptive lymphocyte collection in DLBCL‐NOS patients intended to undergo treatment with Tisagenlecleucel.

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Optimization of lymphapheresis for manufacturing autologous CAR-T cells

Cited by 6 publications

References 20 publications

Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

Get Off on the Right Foot: How to Plan an Efficient Leukocytapheresis to Collect T Cells for CAR T-Cell Manufacturing

Collection of peripheral blood mononucleated cells for chronic graft-versus-host disease immunology research: safety and effectiveness of leukapheresis in 132 patients

Apheresis for chimeric antigen receptor T‐cell production in adult lymphoma patients

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