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Review
. 2019 Jan 22:11:2155179018822781.
doi: 10.1177/2155179018822781. eCollection 2019.

Approval of First CAR-Ts: Have we Solved all Hurdles for ATMPs?

Diane Seimetz  1 , Karl Heller  1 , Jan Richter  2
Affiliations
Review

Approval of First CAR-Ts: Have we Solved all Hurdles for ATMPs?

Diane Seimetz et al. Cell Med. .

Abstract

T cells are known as the most potent killer cells of the immune system, designed by nature to prevent unwanted challenges. The first class of therapeutic products harnessing the power of T cells for target-specific treatment of oncological diseases was bispecific antibodies. The first T-cell engaging bispecific antibodies that obtained approval were catumaxomab and blinatumomab1,2. Eight years later, the first chimeric antigen receptor (CAR)-T cells received regulatory approval3. CAR-T cells are the cellular interpretation of T-cell engaging therapies and have shown remarkable clinical results. CAR-T cells belong to the regulatory group of advanced therapy medicinal products (ATMPs). Due to the cell-/gene-based complex nature, ATMPs are far more challenging to develop than other, more defined, medicinal products. Despite very encouraging clinical results, there have been many set-backs in the development of ATMPs during the past 20 years. Therefore, the approval of the first two CAR-Ts KYMRIAH and YESCARTA is highly encouraging for the field. In this article we review the current landscape of CAR-Ts as a special class of ATMPs. This comprises the pathway to approval including the use of dedicated regulatory tools and challenges that were faced during the procedure. Furthermore, we highlight important future trends in the field.

Keywords: ATMP; CAR-T; PRIME; RMAT; genome editing; regulatory strategy.

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Conflict of interest statement

Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Overview of the status of ATMP and CAR-T products approved in the EU, as of October 2018.
Figure 2.
Figure 2.
Overview of clinical trials with CAR-T products worldwide, as of September 2018, based on data from clinicaltrials.gov.
Figure 3.
Figure 3.
Regulatory tools to consider and integrate into overall US development strategy. Abbreviations: A, approval/authorization; CMC, chemistry manufacturing and control development; I, Phase I clinical development; II, Phase II clinical development; III, Phase III clinical development; L, launch; LCM, life cycle management; NC, non-clinical development; R&D, research and development.
Figure 4.
Figure 4.
CAR-Ts target cell surface antigens [Figure was kindly provided by Medigene].
Figure 5.
Figure 5.
TCRs target the intracellular antigen repertoire [Figure was kindly provided by Medigene].
See this image and copyright information in PMC

References

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