AACR 2022 Poster 617

MEK Inhibitor Rescued the Efficacy of PD-1 Blocker in STK11/LKB1 Mutated Colorectal Cancer Model

Demi X. Liu, Jun Zhou, Chenpan Nie, Annie An, Henry Q.X. Li, Jessie J.J.Wang, Crown Bioscience Inc., 
16550 West Bernardo Drive, Building 5, Suite 525, San Diego, CA 92127

The mechanism of action of primary resistance to PD-1 blockade is largely unknown, however STK11/LKB1 alterations have been reported to have a significant role in primary resistance to PD-1/PD-L1 axis inhibitors in KRAS-mutant lung adenocarcinoma1-3. It is important to identify treatments which can rescue the efficacy of PD-1 blocker in STK11/LKB1-mutant patients. We have developed a STK11 knockout (KO) model using the CT26 colorectal cancer syngeneic line which harbors a KRAS mutation and evaluated the response to PD-1 alone and in combination with MEK inhibitors.

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• Generation of a CT26-STK11 KO cell line valuable for the evaluation of PD-1 blocker and MEK inhibitors in STK11/LKB1 deficient tumors
  
  
• Why the anti-PD-1 efficacy observed in CT26-WT tumors was abolished in CT26-STK11 KO tumors
  
  
• The effect of MEK inhibitor, trametinib, on G-MDSC, CD8+ T cell infiltration and PD-1 blocker efficacy in CT26-STK11 KO tumors
• The effect of combination treatment of MEK inhibitors, such as trametinib, with anti-PD-1 antibody on CT26-STK11 KO tumor growth

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