Driving CARs on the uneven road of antigen heterogeneity in solid tumors Journal Article

   


Authors: Chen, N.; Li, X.; Chintala, N. K.; Tano, Z. E.; Adusumilli, P. S.
Article Title: Driving CARs on the uneven road of antigen heterogeneity in solid tumors
Abstract: Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity. © 2018 Elsevier Ltd
Keywords: immunohistochemistry; cancer chemotherapy; review; pancreas cancer; binding affinity; antigen expression; cell proliferation; protein targeting; carcinoembryonic antigen; epidermal growth factor receptor; epidermal growth factor receptor 2; lung cancer; tumor antigen; regulatory t lymphocyte; cellular immunity; chimeric antigen receptor; mucin 1; density; antigen binding; antigen structure; prostate stem cell antigen; t lymphocyte activation; single chain fragment variable antibody; mesothelin; programmed death 1 receptor; protein polymorphism; tumor microenvironment; receptor upregulation; tumor escape; human; myeloid-derived suppressor cell
Journal Title: Current Opinion in Immunology
Volume: 51
ISSN: 0952-7915
Publisher: Elsevier Inc.  
Date Published: 2018-04-01
Start Page: 103
End Page: 110
Language: English
DOI: 10.1016/j.coi.2018.03.002
PROVIDER: scopus
PUBMED: 29554494
PMCID: PMC5943172
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85043992550&doi=10.1016%2fj.coi.2018.03.002&partnerID=40&md5=441e2ec887580ec60c7e921a1faf7119
Notes: Review -- Export Date: 2 April 2018 -- Source: Scopus
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MSK Authors
  1. Prasad S Adusumilli
    496 Adusumilli
  2. Navin Kumar Chintala
    27 Chintala
  3. Nan Chen
    4 Chen
  4. Zachary Tano
    11 Tano
  5. Xiaoyu Li
    9 Li
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