Autologous CAR T-cell therapies supply chain: challenges and opportunities?

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Abstract

Chimeric antigen receptor (CAR) T cells are considered a potentially disruptive cancer therapy, showing highly promising results. Their recent success and regulatory approval (both in the USA and Europe) are likely to generate a rapidly increasing demand and a need for the design of robust and scalable manufacturing and distribution models that will ensure timely and cost-effective delivery of the therapy to the patient. However, there are challenging tasks as these therapies are accompanied by a series of constraints and particularities that need to be taken into consideration in the decision-making process. Here, we present an overview of the current state of the art in the CAR T cell market and present novel concepts that can debottleneck key elements of the current supply chain model and, we believe, help this technology achieve its long-term potential.

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Fig. 1: Map of clinical trials1 currently on chimeric antigen receptor T cell therapies (Source: ClinicalTrials.gov).
Fig. 2: Visual representation of the advanced therapies treatment centres in the UK.
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Fig. 5: Representation of the “dynamic” supply chain concept, where the supply chain network changes with respect to the increasing demand.

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Acknowledgements

The authors would like to acknowledge expert opinion received through multiple conversations with the User Steering Committee of the Future Targeted Healthcare Manufacturing Hub. Funding from the UK Engineering & Physical Sciences Research Council (EPSRC) for the Future Targeted Healthcare Manufacturing Hub hosted at University College London with UK university partners is gratefully acknowledged (Grant Reference: EP/P006485/1). Financial and in-kind support from the consortium of industrial users and sector organisations is also acknowledged.

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Correspondence to Maria M. Papathanasiou.

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Supplementary information

Appendix A

Appendix A

For the patient population forecast studies, we assume a constant average growth of approximately 0.4% [34] and constant incidence rates per 100,000 people ((HMRN (Haematological Malignancy Research Network), 2018)), as presented in Table A.1 in the supplementary information. Based on these assumptions, we present indicative projections (Table A.2, supplementary information) for the liquid cancer patient population in the UK for the next 15 years. In order to estimate the patient population, we only consider liquid cancer types as currently CAR T therapies are considered to be more advanced in that space. Furthermore, the types of liquid cancer here have been chosen based on data availability. Patient population numbers for types not present in the current set are either scarcely provided or not available.

The three final rows of Table A.2 (please see supplementary information) represent: (1) the total number of patients with liquid cancer in the UK for the next 15 years, (2) a scenario where estimates are 20% lower and (3) a scenario where estimates are 20% higher. Figure A1 of the supplementary information represents the ±20% case. Nevertheless, CAR T cell therapies will most probably not be the first line of therapy, therefore limiting the number of eligible patients. Figure A.1 (please see supplementary information) illustrates a potential scenario, where only 10% of the total patient population will be eligible for CAR T cell therapy treatment. Despite this constraint, patient numbers are estimated to increase almost fivefold by 2031, thus challenging CART manufacturing and supply chain scale up.

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Papathanasiou, M.M., Stamatis, C., Lakelin, M. et al. Autologous CAR T-cell therapies supply chain: challenges and opportunities?. Cancer Gene Ther (2020) doi:10.1038/s41417-019-0157-z

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