Display options
Share it on

Cancer Immunol Res. 2021 Sep;9(9):1047-1060. doi: 10.1158/2326-6066.CIR-20-0470. Epub 2021 Jul 09.

Rationally Designed Transgene-Encoded Cell-Surface Polypeptide Tag for Multiplexed Programming of CAR T-cell Synthetic Outputs.

Cancer immunology research

Adam J Johnson, Jia Wei, James M Rosser, Annette Künkele, Cindy A Chang, Aquene N Reid, Michael C Jensen

Affiliations

  1. Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington.
  2. Seattle Children's Therapeutics, Seattle, Washington.
  3. Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington. [email protected].
  4. Department of Pediatrics, University of Washington, Seattle, Washington.
  5. Department of Bioengineering, University of Washington, Seattle, Washington.

PMID: 34244298 PMCID: PMC8415133 DOI: 10.1158/2326-6066.CIR-20-0470

Abstract

Synthetic immunology, as exemplified by chimeric antigen receptor (CAR) T-cell immunotherapy, has transformed the treatment of relapsed/refractory B cell-lineage malignancies. However, there are substantial barriers-including limited tumor homing, lack of retention of function within a suppressive tumor microenvironment, and antigen heterogeneity/escape-to using this technology to effectively treat solid tumors. A multiplexed engineering approach is needed to equip effector T cells with synthetic countermeasures to overcome these barriers. This, in turn, necessitates combinatorial use of lentiviruses because of the limited payload size of current lentiviral vectors. Accordingly, there is a need for cell-surface human molecular constructs that mark multi-vector cotransduced T cells, to enable their purification

©2021 American Association for Cancer Research.

References

  1. Blood. 2010 Nov 25;116(22):4532-41 - PubMed
  2. Biol Blood Marrow Transplant. 2010 Sep;16(9):1245-56 - PubMed
  3. Pharmaceutics. 2020 Feb 24;12(2): - PubMed
  4. In Vitro Cell Dev Biol. 1986 Dec;22(12):689-94 - PubMed
  5. Nat Med. 2018 Jan;24(1):20-28 - PubMed
  6. Immunol Rev. 2015 Jan;263(1):68-89 - PubMed
  7. Cancer Immunol Res. 2015 Feb;3(2):125-35 - PubMed
  8. Br J Haematol. 2018 Nov;183(3):364-374 - PubMed
  9. Blood. 2011 Feb 10;117(6):1888-98 - PubMed
  10. Blood. 2014 Jun 19;123(25):3895-905 - PubMed
  11. Cancer Immunol Immunother. 2010 Jun;59(6):851-62 - PubMed
  12. PLoS One. 2013 Dec 17;8(12):e82742 - PubMed
  13. PLoS One. 2013 Jun 06;8(6):e65519 - PubMed
  14. Cancer Gene Ther. 2017 Mar;24(3):121-129 - PubMed
  15. J Clin Invest. 2016 Aug 1;126(8):3036-52 - PubMed
  16. Blood. 2011 Aug 4;118(5):1255-63 - PubMed
  17. Cancer Discov. 2018 Oct;8(10):1219-1226 - PubMed
  18. Front Oncol. 2019 Apr 24;9:297 - PubMed
  19. Blood. 2018 Jun 14;131(24):2621-2629 - PubMed
  20. Immunol Rev. 2014 Jan;257(1):107-26 - PubMed
  21. Mol Ther. 2003 Jul;8(1):29-41 - PubMed
  22. Annu Rev Pharmacol Toxicol. 2016;56:59-83 - PubMed
  23. Immunol Rev. 2014 Jan;257(1):127-44 - PubMed
  24. Nature. 2003 Feb 13;421(6924):756-60 - PubMed
  25. Cell. 2016 Oct 6;167(2):419-432.e16 - PubMed
  26. Mol Immunol. 2012 Jul;51(3-4):263-72 - PubMed
  27. Nat Med. 2019 Sep;25(9):1341-1355 - PubMed
  28. Int J Biol Sci. 2016 Apr 28;12(6):718-29 - PubMed
  29. Cell. 2016 Feb 11;164(4):770-9 - PubMed
  30. Blood. 2006 Mar 15;107(6):2294-302 - PubMed
  31. Nature. 2017 May 24;545(7655):423-431 - PubMed
  32. Bioprocess Int. 2012 Feb;10(2):32-43 - PubMed
  33. J Immunother Cancer. 2017 May 16;5:42 - PubMed
  34. Cancer Immunol Res. 2016 Jun;4(6):498-508 - PubMed
  35. Mol Immunol. 2013 Nov;56(1-2):1-11 - PubMed
  36. Oncotarget. 2019 Dec 17;10(66):7080-7095 - PubMed
  37. J Clin Invest. 2019 Mar 12;129(5):2123-2132 - PubMed
  38. Nat Methods. 2009 May;6(5):343-5 - PubMed
  39. Clin Cancer Res. 2013 Jun 15;19(12):3153-64 - PubMed
  40. Blood. 2014 Aug 21;124(8):1277-87 - PubMed

Publication Types

Grant support