Anti-PD1 Drug-resistant Tumor Models

Patient Derived Xenograft (PDX) Mouse Models and Efficacy Services
Leukemias PDXStomach Cancer PDXPancreatic Cancer PDXOvarian Cancer PDXLung cancer PDXColorectal Cancer PDXBreast Cancer PDXBladder Cancer PDX
Humanized Immune Checkpoint Mouse Models and Efficacy Services
Anti-PD1 Drug-resistant Tumor ModelsIn Vivo Efficacy Studies Using TIGIT Humanized ModelsPDL1 Humanized Mouse ModelPD1 Humanized Mouse ModelsOX40 Humanized Mouse ModelsIn vivo Efficacy Test in LAG3 Humanized Mouse ModelsIn vivo Efficacy Test in GITR Humanized Mouse ModelCTLA4 Humanized Mouse ModelsIn vivo Efficacy Test in CD137 Humanized Models

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.

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Fig1. Keytruda-induced drug resistance model in CT26

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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.

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


3. Natural drug-resistant strain model

KPC: TIL analysis

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

 

Pan02: Drug efficacy data

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

 

B16F10: Drug efficacy data and TIL analysis

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

 

LLC: TIL analysis

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

 

4T1: Drug efficacy data and TIL analysis

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

 

EMT6: Drug efficacy data and TIL analysis 

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

 

RENCA: Drug efficacy data and TIL analysis

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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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