TY - JOUR
T1 - Advancing CAR T cell therapy through the use of multidimensional omics data
AU - Yang, Jingwen
AU - Chen, Yamei
AU - Jing, Ying
AU - Green, Michael R.
AU - Han, Leng
N1 - Funding Information:
The work of the authors is supported by the US NIH (grants R01HG011633 and R01CA262623 to L.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. M.R.G. is a Scholar of the Leukaemia and Lymphoma Society. The authors regret that page limitations have prevented them from including all the relevant studies in this Review. Draft figures for this manuscript were created with BioRender.com.
Funding Information:
The work of the authors is supported by the US NIH (grants R01HG011633 and R01CA262623 to L.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. M.R.G. is a Scholar of the Leukaemia and Lymphoma Society. The authors regret that page limitations have prevented them from including all the relevant studies in this Review. Draft figures for this manuscript were created with BioRender.com.
Funding Information:
M.R.G. has stock ownership interest in KDAc Therapeutics, receives funding from Abbvie, Allogene, Kite/Gilead and Sanofi, and has received honoraria from Tessa Therapeutics. J.Y., Y.C., Y.J. and L.H. declare no competing interests.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/4
Y1 - 2023/4
N2 - Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, we summarize the multidimensional cellular and molecular profiling technologies that have been used to advance our mechanistic understanding of CAR T cell therapies. In addition, we discuss current applications and potential strategies leveraging multi-omics data to identify optimal target antigens and other molecular features that could be exploited to enhance the antitumour activity and minimize the toxicity of CAR T cell therapy. Indeed, fully utilizing multi-omics data will provide new insights into the biology of CAR T cell therapy, further accelerate the development of products with improved efficacy and safety profiles, and enable clinicians to better predict and monitor patient responses.
AB - Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of certain haematological malignancies, challenges remain in optimizing CAR designs and cell products, improving response rates, extending the durability of remissions, reducing toxicity and broadening the utility of this therapeutic modality to other cancer types. Data from multidimensional omics analyses, including genomics, epigenomics, transcriptomics, T cell receptor-repertoire profiling, proteomics, metabolomics and/or microbiomics, provide unique opportunities to dissect the complex and dynamic multifactorial phenotypes, processes and responses of CAR T cells as well as to discover novel tumour targets and pathways of resistance. In this Review, we summarize the multidimensional cellular and molecular profiling technologies that have been used to advance our mechanistic understanding of CAR T cell therapies. In addition, we discuss current applications and potential strategies leveraging multi-omics data to identify optimal target antigens and other molecular features that could be exploited to enhance the antitumour activity and minimize the toxicity of CAR T cell therapy. Indeed, fully utilizing multi-omics data will provide new insights into the biology of CAR T cell therapy, further accelerate the development of products with improved efficacy and safety profiles, and enable clinicians to better predict and monitor patient responses.
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U2 - 10.1038/s41571-023-00729-2
DO - 10.1038/s41571-023-00729-2
M3 - Review article
C2 - 36721024
AN - SCOPUS:85147101531
SN - 1759-4774
VL - 20
SP - 211
EP - 228
JO - Nature Reviews Clinical Oncology
JF - Nature Reviews Clinical Oncology
IS - 4
ER -