Optimizing CAR-T treatment: A T2EVOLVE guide to raw and starting material selection

Molecular Therapy, vol. 33, pp. 847–865

Abstract

Chimeric antigen receptor (CAR)-T cell products, classified as Advanced Therapy Medicinal Products (ATMPs), have shown promising outcomes in cancer immunotherapy. The quality of raw and starting materials used in manufacturing is critical to ensure the efficacy and safety of CAR-T cell products and depends primarily on the selection of the right materials and the right suppliers. It is essential to consider a long-term strategy when selecting raw and starting materials to prevent delays in the supply of innovative, high-quality, and safe therapies to patients. A thorough assessment will allow developers not only to select suppliers who comply with regulatory requirements but also to ensure a sustainable supply of materials throughout the development and the commercial phases. A careful selection of materials and suppliers can avoid the need of comparability studies due to changes in the supply of materials, impacting costs and causing significant delays in development and treatment readiness for patients. This work, coordinated by the T 2 EVOLVE IMI consortium, provides guidance for the selection and handling of raw and starting materials. By following these suggestions, developers can ensure that they use high quality raw and starting materials through the product development and life cycle, resulting in safe and effective CAR-T therapies for patients.

Authors 18

1. Sergio Navarro Velázquez corresponding

   Hospital Clínic de Barcelona

   Affiliation as printed

   Hospital Clínic de Barcelona, Secció d'Immunoterapia - Servei d'Immunologia, Barcelona, Spain. Electronic address: senavarro@clinic.cat

2. Carole Moukheiber corresponding

   Institut de Recherches Internationales Servier (France)

   Affiliation as printed

   Institut de Recherches Internationales Servier, Gif-sur-Yvette, France. Electronic address: carole.moukheiber@servier.com

3. Susana Inogés Sancho corresponding

   Clinica Universidad de Navarra

   Affiliation as printed

   Clínica Universidad de Navarra, Hematología- Área de Terapia Celular, Pamplona, Spain. Electronic address: sinoges@unav.es

4. Ascensión López-Dı́az de Cerio

   Clinica Universidad de Navarra

   Affiliation as printed

   Clínica Universidad de Navarra, Hematología- Área de Terapia Celular, Pamplona, Spain

5. Carmen Sanges

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

6. Toshimitsu Tanaka

   Astellas Pharma (Japan)

   Affiliation as printed

   Astellas Pharma Inc, Tokyo, Japan

7. Sylvain Arnould

   Institut de Recherches Internationales Servier (France)

   Affiliation as printed

   Institut de Recherches Internationales Servier, Gif-sur-Yvette, France

8. Javier Briones

   Hospital de Sant Pau

   Affiliation as printed

   Hospital de Sant Pau, Hematology Department, Barcelona, Spain

9. Harry Dolstra

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Radboud University Medical Center, Department of Laboratory Medicine, Nijmegen, the Netherlands

10. Michael Hudecek

    Universitätsklinikum Würzburg · Fraunhofer Institute for Cell Therapy and Immunology

    Affiliation as printed

    Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany; Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

11. Rashmi Choudhary
    Affiliation as printed

    Takeda Development Centers Americas, Inc, Lexington, MA, USA

12. Inga Schapitz

    Bayer (Germany)

    Affiliation as printed

    Bayer Vital GmbH, Leverkusen, Germany

13. Manel Juan

    Hospital Clínic de Barcelona

    Affiliation as printed

    Hospital Clínic de Barcelona, Secció d'Immunoterapia - Servei d'Immunologia, Barcelona, Spain

14. Nina Worel

    Medical University of Vienna

    Affiliation as printed

    Medical University of Vienna, Department of Transfusion Medicine and Cell Therapy, Vienna, Austria

15. Delphine Ammar Aachen Astellas Pharma B.V

    Astellas Pharma (Netherlands)

    Affiliation as printed

    Astellas Pharma B.V., Leiden, the Netherlands

16. Maik Luu

    University of Würzburg · Universitätsklinikum Würzburg

    Affiliation as printed

    Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

17. Hélène Trebeden‐Negre

    Institut de Recherches Internationales Servier (France)

    Affiliation as printed

    Institut de Recherches Internationales Servier, Gif-sur-Yvette, France

18. Paul Franz corresponding

    Fraunhofer Institute for Cell Therapy and Immunology

    Affiliation as printed

    Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany. Electronic address: paul.franz@izi.fraunhofer.de