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Decentralized manufacturing of anti CD19 CAR-T cells using CliniMACS Prodigy®: real-world experience and cost analysis in India

Bone Marrow Transplantation volume 58, pages 160–167 (2023)Cite this article

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Abstract

Chimeric Antigen Receptor (CAR) T cell therapy is an accepted standard of care for relapsed/refractory B cell malignancies. However, the high cost of existing industry-driven centralized production makes this therapy unaffordable in low and middle-income countries. Decentralized or point of care manufacturing has the potential to overcome some of these challenges. Here we demonstrate a decentralized manufacturing process for anti-CD19-CAR-T cells using a fully automated closed system (Miltenyi CliniMACS Prodigy®) is feasible in a developing country setting. Validation run data, as part of a pre-clinical trial safety evaluation, demonstrates the successful and robust manufacturing of anti-CD19 CAR-T cells with T cell expansion of 25 to 47-fold. The median transduction efficiency was 48.8%, with a median viability of 98% and fulfillment of all standard release criteria assays for clinical application. Evaluation of production costs in an academic, not for profit setting in India provide a benchmark for low and middle-income pricing which could greatly increase access to this therapy. Based on our analysis, the cost per product would be approximately $35,107 US dollars. Our data highlights the safety, efficacy, and reproducibility of the process for use in planned future clinical trials.

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Fig. 1: Workflow of manufacturing CD19 CAR-T cells using CliniMACS Prodigy®.
Fig. 2: Characterization of anti-CD19 CAR-T cells manufactured using CliniMACS Prodigy® system.
Fig. 3: Immunophenotypic characterization of CAR-T cells and their differentiation status.
Fig. 4: Cytokine analysis of CAR-T cells exposed to target/non-target cells.
Fig. 5: CAR-T cells showed a potent antitumor activity in-vitro.
Fig. 6: Cost analysis per run for manufacturing CAR-T cells using CliniMACS Prodigy®.

Data availability

All data are available upon request.

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Acknowledgements

The authors thank Dr. Nedunchezhian, Cytocare Technologies, Bengaluru, India, for support in manufacturing CAR-T cells.

Funding

This study is supported by an Indian Council of Medical Research (ICMR) grant (91/06/2020-TFGTR/BMS), New Delhi, India.

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Author notes

  1. Boro Dropulic

    Present address: Caring Cross, Gaithersburg, MD, USA

Authors and Affiliations

  1. Department of Haematology, Christian Medical College, Vellore, India

    Hamenth Kumar Palani, Arun Kumar Arunachalam, Mohammed Yasar, Arvind Venkatraman, Uday Kulkarni, Sharon Anbumalar Lionel, Sushil Selvarajan, Anu Korula, Aby Abraham, Biju George & Vikram Mathews

  2. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Jennifer E. Adair

  3. Caring Cross, Gaithersburg, MD, USA

    Rimas Orentas

  4. Lentigen, Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, USA

    Boro Dropulic

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  1. Hamenth Kumar Palani
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  14. Vikram Mathews
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Contributions

HKP, VM, BD, RO, JA conceived the study design. HKP, AKA, MY, AV, UK, SAL, SS, AK, AA, BG performed research, clinical data accrual and data analysis. HKP, VM, JA wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Vikram Mathews.

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Palani, H.K., Arunachalam, A.K., Yasar, M. et al. Decentralized manufacturing of anti CD19 CAR-T cells using CliniMACS Prodigy®: real-world experience and cost analysis in India. Bone Marrow Transplant 58, 160–167 (2023). https://doi.org/10.1038/s41409-022-01866-5

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