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Antibody Therapy in Oncology

MoBi/OSP-Suite Version 10

Length: 17 Check-Up-Points

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You will learn how to set up a simulation for large molecules (proteins and peptides) in PK-Sim. The modeled compound is an antibody-drug conjugate (ADC) applied for the treatment of prostate cancer. The ADC consists of an antibody against the transmembrane protein TenB2 (TMEFF2) and the antimitotic toxin monomethyl auristatin E (MMAE), which is attached to the antibody by a linker. The antibody in the ADC has high affinity to the TMEFF2 receptor making it a suitable substance to target prostate cancer cells over-expressing TMEFF2, while the MMAE toxin is used to neutralize/kill such cancer cells.

You will set up a combined model for the simulation of the ADC and the released toxophore (i.e. the MMAE toxin) including receptor dynamics and internalization of the ADC-receptor complex. Here, you will learn how to:
1. export a PK-Sim model to MoBi.
2. integrate the reactions for receptor dynamics and internalization of the ADC-TMEFF2 complex (import “ReactionsADCModel.pkml).
4. simulate and analyze the behavior of the toxophore concentration in venous blood and the TMEFF2 concentration in the interstitium of the lung for different doses
5. investigate how naked antibodies change the result.