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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.

Fig3. Keytruda efficacy test in subcutaneous tumor-bearing CT26 and CT26-mB2m KO models of BALB/c-hPD1 mice

  1. Natural drug-resistant strain model

KPC: TIL analysis

Fig4. Subcutaneous inoculation of KPC cell line in C57BL/6J mice

Pan02: Drug efficacy data

Fig5. Subcutaneous inoculation of Pan02 cell line in C57BL/6J mice

B16F10: Drug efficacy data and TIL analysis

Fig6. Subcutaneous inoculation of B16F10 cell line in B6-hPD1/hLAG3 mice

LLC: TIL analysis

Fig7. Subcutaneous inoculation of LLC cell line in C57BL6-hPD1 mice

4T1: Drug efficacy data and TIL analysis

Fig8. Subcutaneous inoculation of 4T1 cell line in Balb/c-hPD1hTIGIT mice

EMT6: Drug efficacy data and TIL analysis 

Fig9. Subcutaneous inoculation of EMT6 cell line in BALB/c-hPDL1 mice

RENCA: Drug efficacy data and TIL analysis

Fig10. Subcutaneous inoculation of RENCA cell line in BALB/c-hPD1/hTIGIT mice

Characteristics and Application Scenarios of Various Drug Resistance Models

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