, Volume 33, Issue 3, pp 275–284 | Cite as

Immunogenicity of Chimeric Antigen Receptor T-Cell Therapeutics

  • Boris GorovitsEmail author
  • Eugen Koren
Review Article


Chimeric antigen receptor (CAR) T-cell immunotherapy has gained significant attention in the past decade due to its considerable potential in the treatment of various types of malignancies, particularly hematological. While success has been achieved in a number of studies, and two CAR-T-cell products were recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (YESCARTA®, KYMRIAH®), this treatment modality continues to present challenges for clinical development. One major potential side effect is the ability of CAR-T products to induce host immune responses. Immunogenicity induction risk factors have been shown to be associated with the presence of non-human or partially human sequences in the CAR construct, suicide domain, or other components of the CAR-T, and also with the presence of residual viral proteins or other non-human origin proteins utilized as part of the gene editing step of CAR-T production. Both humoral (antibody-based) and cellular-type responses have been described, leading to various degrees of impact on CAR-T expansion and persistence, and therefore the overall safety and clinically meaningful response of the treatment. In this article we discuss various types of immune responses specific to CAR-T therapy, their impact on treatment outcome, and methodologies used to detect them.


Compliance with Ethical Standards


No funding was received in the preparation of this review.

Conflict of interest

Boris Gorovits is employed by the Pfizer Inc. which in the past has been involved in the development of CAR-T therapeutics. Eugen Koren is employed by the Precision for Medicine, which supports development of CAR-T therapeutics.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pfizer Inc.AndoverUSA
  2. 2.Precision for MedicineRedwood CityUSA

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