Accelerating development of engineered T cell therapies in the EU: current regulatory framework for studying multiple product versions and T2EVOLVE recommendations

Front Immunol. 2023 Nov 24:14:1280826. doi: 10.3389/fimmu.2023.1280826. eCollection 2023.

Abstract

To accelerate the development of Advanced Therapy Medicinal Products (ATMPs) for patients suffering from life-threatening cancer with limited therapeutic options, regulatory approaches need to be constantly reviewed, evaluated and adjusted, as necessary. This includes utilizing science and risk-based approaches to mitigate and balance potential risks associated with early clinical research and a more flexible manufacturing paradigm. In this paper, T2EVOLVE an Innovative Medicine Initiative (IMI) consortium explores opportunities to expedite the development of CAR and TCR engineered T cell therapies in the EU by leveraging tools within the existing EU regulatory framework to facilitate an iterative and adaptive learning approach across different product versions with similar design elements or based on the same platform technology. As understanding of the linkage between product quality attributes, manufacturing processes, clinical efficacy and safety evolves through development and post licensure, opportunities are emerging to streamline regulatory submissions, optimize clinical studies and extrapolate data across product versions reducing the need to perform duplicative studies. It is worth noting that this paper is focusing on CAR- and TCR-engineered T cell therapies but the concepts may be applied more broadly to engineered cell therapy products (e.g., CAR NK cell therapy products).

Keywords: advanced therapy medicinal products (ATMP); clinical development; engineered T cell therapies; multiple product candidates; parent-child approach.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell- and Tissue-Based Therapy*
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes

Substances

  • Receptors, Antigen, T-Cell

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 945393. This Joint Undertaking receives support from the European Union´s Horizon 2020 research and innovation program and EFPIA.