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Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity.

Talar TokatlianGrace E AsuelimeMartin S NaradikianJee-Young MockMark E DarisAaron D MartinDora Toledo WarshaviakAlexander KambAgnes E Hamburger
Published in: Cancer research communications (2022)
We report an effort to generate high potency, selective CARs directed at mutant KRAS peptides. Although the heavily optimized CARs maintain high selectivity against wild-type KRAS, they lose selectivity against other KRAS-related peptides derived from human proteins. To our knowledge, this work is the first to examine the trade-off between potency and selectivity with regard to KRAS pMHC-directed CARs, illustrating the challenge to achieve both sufficient potency and high selectivity.
Keyphrases
  • wild type
  • structural basis
  • healthcare
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  • induced pluripotent stem cells