TY - JOUR
T1 - Dissecting the Tumor–Immune Landscape in Chimeric Antigen Receptor T-cell Therapy
T2 - Key Challenges and Opportunities for a Systems Immunology Approach
AU - Chen, Gregory M.
AU - Azzam, Andrew
AU - Ding, Yang Yang
AU - Barrett, David M.
AU - Grupp, Stephan A.
AU - Tan, Kai
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/7/15
Y1 - 2020/7/15
N2 - The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint. Whereas cancer consortia have traditionally focused on the genomic, transcriptomic, epigenomic, and proteomic landscape of cancer cells, there is an increasing need to expand studies to analyze the interactions between tumor, immune, and stromal cell populations in their relevant anatomical and functional compartments. Here, we focus on the promising application of systems biology to address key challenges in CAR T-cell therapy, from understanding the mechanisms of therapeutic resistance in hematologic and solid tumors to addressing important clinical challenges in biomarker discovery and therapeutic toxicity. We propose a systems biology view of key clinical objectives in CAR T-cell therapy and suggest a path forward for a biomedical discovery process that leverages modern technological approaches in systems biology.
AB - The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint. Whereas cancer consortia have traditionally focused on the genomic, transcriptomic, epigenomic, and proteomic landscape of cancer cells, there is an increasing need to expand studies to analyze the interactions between tumor, immune, and stromal cell populations in their relevant anatomical and functional compartments. Here, we focus on the promising application of systems biology to address key challenges in CAR T-cell therapy, from understanding the mechanisms of therapeutic resistance in hematologic and solid tumors to addressing important clinical challenges in biomarker discovery and therapeutic toxicity. We propose a systems biology view of key clinical objectives in CAR T-cell therapy and suggest a path forward for a biomedical discovery process that leverages modern technological approaches in systems biology.
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U2 - 10.1158/1078-0432.CCR-19-3888
DO - 10.1158/1078-0432.CCR-19-3888
M3 - Review article
C2 - 32127393
AN - SCOPUS:85087843419
SN - 1078-0432
VL - 26
SP - 3505
EP - 3513
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -