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Updated: Nov 16, 2025
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Immunogenicity of CAR T cells in cancer therapy
Dimitrios L Wagner1,2, Enrico Fritsche1, Michael A Pulsipher3
1Berlin Center for Advanced Therapies (BeCAT) and Berlin Institute of Health (BIH) Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
Patient-derived T cells genetically reprogrammed to express CD19-specific chimeric antigen receptors (CARs) have shown remarkable clinical responses and are commercially available for the treatment of patients with certain advanced-stage B cell malignancies. Nonetheless, several trials have revealed pre-existing and/or treatment-induced immune responses to the mouse-derived single-chain variable fragments included in these constructs. These responses might have contributed to both treatment failure and the limited success of redosing strategies observed in some patients. Data from early phase clinical trials suggest that CAR T cells are also associated with immunogenicity-related events in patients with solid tumours. Generally, the clinical implications of anti-CAR immune responses are poorly understood and highly variable between different CAR constructs and malignancies. These observations highlight an urgent need to uncover the mechanisms of immunogenicity in patients receiving CAR T cells and develop validated assays to enable clinical detection. In this Review, we describe the current clinical evidence of anti-CAR immune responses and discuss how new CAR T cell technologies might impact the risk of immunogenicity. We then suggest ways to reduce the risks of anti-CAR immune responses to CAR T cell products that are advancing towards the clinic. Finally, we summarize measures that investigators could consider in order to systematically monitor and better comprehend the possible effects of immunogenicity during trials involving CAR T cells as well as in routine clinical practice.
Insights
Immune responses to chimeric antigen receptor (CAR) T cells, particularly their mouse-derived components, can hinder treatment effectiveness in B cell malignancies and solid tumors. Understanding and mitigating these anti-CAR immune responses is crucial for improving CAR T cell therapy outcomes.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptor (CAR) T cell therapy, using genetically engineered T cells, has shown success in treating B cell malignancies.
- Immune responses against the mouse-derived components of CARs are increasingly recognized as a challenge.
- These anti-CAR immune responses may lead to treatment failure and limit redosing efficacy.
Purpose of the Study:
- To review current clinical evidence of anti-CAR immune responses.
- To discuss how novel CAR T cell technologies may influence immunogenicity.
- To propose strategies for reducing anti-CAR immune responses and monitoring their clinical impact.
Main Methods:
- Review of clinical trial data and scientific literature on CAR T cell immunogenicity.
- Analysis of emerging CAR T cell technologies and their potential impact on immune responses.
- Synthesis of current understanding and future directions for managing anti-CAR immunity.
Main Results:
- Pre-existing and treatment-induced immune responses to CAR T cells are observed in patients with both hematological malignancies and solid tumors.
- The clinical significance of anti-CAR immune responses is variable and not fully understood.
- New CAR T cell designs may alter the immunogenicity profile.
Conclusions:
- There is an urgent need to understand the mechanisms of anti-CAR immune responses and develop assays for their detection.
- Strategies to mitigate immunogenicity are essential for advancing CAR T cell therapies.
- Systematic monitoring of anti-CAR immune responses is recommended in clinical trials and practice.
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