Anticuerpo humano dirigido por TIGIT modula la regulación de linfocitos T y la función efectora celular

AUTORES:

Alyson J. Smith, Weiping Zeng, Bryan Grogan, Jane Haass, Amber Blackmarr, Robert Thurman, Scott Peterson, Shyra J. Gardai Research Department, Seattle Genetics Inc., Bothell, WA

AÑO:

 2019

AACR 2019

Covance was mentioned within in the Seattle Genentics poster they presented at the AACR 2019 Conference. Stated under the "SGN-TIGIT displays strong anti-tumor efficacy" figures:

"SGN-TIGIT treatment in CT26 and A20 syngeneic models cured 50 % and 33 % of animals, respectively. SGN-TIGIT in the MC38, E0771, EMT6, and an alternative CT26 model, run by Covance, resulted in partial responses (PR), seen as tumor growth delay."

Introducción y antecedentes

  • TIGIT inhibits T and NK cell function by binding CD155 and CD112, which are upregulated on tumor cells
  • SGN-TIGIT is fully human anti-TIGIT monoclonalantibody (mAb) that has equivalent affinity for human, murine and cynomolgus TIGIT and blocks TIGIT lig and binding
  • SGN-TIGIT mediates ADCC top referentially deplete Tregsinex-vivo PBMC cultures
  • SGN-TIGIT amplifies naïve and memory CD8 T cell responses
  • SGN-TIGIT can result in curative single agent anti-tumor responses in several preclinical models, though its MOA appears distinct from PD-(L)1
  • Models enriched for activated and/or memory CD8 T cell transcripts were positively correlated with curative response