Anti-PD1 Drug-resistant Tumor Models：Three Types of Drug Models and Application Scenarios

The PD-1/PD-L1 axis is a well-known immune checkpoint, High activity within the PD-1/ PD-L1 axis promotes T cell dysfunction. Great progresses are made in recent years to use PD-1/PDL1 blockade therapy in cancer treatment. Studies have shown that primary resistance to anti-PD1 therapies is common, affecting up to 60% of patients in some cancer. Furthermore, it is now becoming apparent that initial responses observed among some patients can be undone by their development of acquired resistance to anti-PD1 therapies. Given the common problem, GemPharmatech has successfully developed a variety of anti-PD1 resistant model.

1.Keytruda-induced resistance model

Through inoculating anti-PD1 drug-sensitive tumor cell lines CT26 and MC38 on hPD1 target humanized mice, followed by induction with Keytruda, drug-resistant tumor strains were isolated and established. These resistant strains were then re-implanted into mice and subjected to drug treatment induction. After multiple cycles of this process, drug-resistant strains were eventually obtained.

Fig1. Keytruda-induced drug resistance model in CT26

Fig2. Keytruda-induced drug resistance model in MC38

2.MHC-I deficiency drug-resistant model

MHC-I (major histocompatibility complex class I), mainly mediates the process of endogenous antigen presentation, and knockout of B2M protein results in MHC-I deficiency.