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Are genetically modified protozoa eligible for ATMP status? Concerning the legal categorization of an oncolytic protozoan drug candidate

Gene Therapy (2024)Cite this article

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Abstract

Neospora caninum is an obligate intracellular protozoan that affects several animal species. It is not pathogenic for humans, and its ability to infect and lyse a variety of cells and stimulate the immune system makes it an interesting drug candidate in oncology. The intrinsic oncolytic properties of N. caninum have been confirmed in several preclinical models. Moreover, it can be modified to improve its safety and/or efficacy against cancer cells. In this study, we propose the legal categorization of this new biological drug candidate and the impact of modifications, notably the integration of a suicide gene, the deletion of a gene allowing its multiplication in healthy cells, and/or the insertion of a gene coding for a therapeutic protein into its genome. When unmodified, N. caninum can be categorized as a biological medicinal product, whereas modifications aimed at increasing its safety classify it as a Somatic Cell Therapy Medicinal Product, and modifications aiming to increase its efficacy or both safety and efficacy make it as a Gene Therapy Medicinal Product. This categorization is fundamental because it determines the guidelines applicable for preclinical development. These guidelines being numerous and complex, we have focused on the key requirements necessary for the development of the future medicinal product.

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Fig. 1: Categorization of the drug candidate Neospora caninum depending on the genetic modifications applied.
Fig. 2: Main guidelines to be used for the development and production of the drug candidate Neospora caninum genetically modified to enhance efficacy.

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Acknowledgements

This work was carried out within the framework of Labex LipSTIC, ANR-11-LABX-0021. We thank the Region Bourgogne - Franche Comté and the FEDER. We thank Dr. Marc Sautour for his help in the phylogenetic analysis.

Funding

We were supported by the Laboratory of Excellence Labex LipSTIC, ANR-11-LABX-0021, the Region Bourgogne - Franche Comté and the FEDER.

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Authors and Affiliations

  1. Faculty of Health Sciences (Pharmacy), University of Burgundy, 7 bd Jeanne d’Arc, 21079, Dijon, Cedex, France

    Mathieu Guerriaud & Evelyne Kohli

  2. CREDIMI Laboratory EA 7532, 4 bd Gabriel, 21000, Dijon, France

    Mathieu Guerriaud

  3. Laboratory of Excellence LipSTIC ANR-11-LABX-0021, Dijon, France

    Mathieu Guerriaud & Evelyne Kohli

  4. Université de Tours, INRAE, ISP, 37380, Tours, France

    Cyril Poupet & Zineb Lakhrif

  5. UMR INSERM/uB/AGROSUP 1231, Team 3 HSP-Pathies, Labelled Ligue Nationale Contre le Cancer, Dijon, France

    Evelyne Kohli

  6. INRAE, Université de Tours, ISP, 37380, Nouzilly, France

    Nathalie Moiré

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Contributions

Mathieu GUERRIAUD: designed and drafted the legal and regulatory part, carried out the legal analysis, selected the key points of the guidelines. He was responsible for coordinating the writting and overseeing the several proofreading sessions. Cyril POUPET: has written the scientific sections on Neospora caninum and has discussed the scientific issues, performed the final proofreading. Zineb LAKHRIF: she has corrected the scientific parts and specifically proofread the parts concerning the protozoa. Evelyne Kohli: she has corrected the scientific parts with regard to immunology and virology, she has widely discussed the links between scientific and legal issues. Nathalie MOIRÉ: has written the scientific sections on Neospora caninum and has discussed the scientific issues, performed the final proofreading.

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Correspondence to Mathieu Guerriaud.

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Guerriaud, M., Poupet, C., Lakhrif, Z. et al. Are genetically modified protozoa eligible for ATMP status? Concerning the legal categorization of an oncolytic protozoan drug candidate. Gene Ther (2024). https://doi.org/10.1038/s41434-024-00445-1

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