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Related Experiment Video

Updated: Nov 23, 2025

Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish

Predicting In Vivo Payloads Delivery using a Blood-brain Tumor-barrier in a Dish

Published on: April 16, 2019

Quantifying ADC bystander payload penetration with cellular resolution using pharmacodynamic mapping.

Eshita Khera¹, Cornelius Cilliers¹, Michael D Smith²

¹Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.

Neoplasia (New York, N.Y.)

|January 1, 2021

Summary

This summary is machine-generated.

Antibody drug conjugates (ADCs) show promise for cancer treatment. This study tracked payload diffusion in tumors, revealing moderate tissue penetration that balances efficacy and uptake for better therapeutic design.

Keywords:

ADC bystander effect Pharmacodynamic marker Primary human tumor xenograft Tumor spheroids Tumor-associated macrophages

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Last Updated: Nov 23, 2025

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Area of Science:

Oncology
Pharmacology
Biotechnology

Background:

Antibody drug conjugates (ADCs) are emerging as a targeted cancer therapy.
Understanding payload diffusion and bystander effects is crucial for ADC efficacy in solid tumors.
Current knowledge on payload penetration distance in tumor tissue remains limited.

Purpose of the Study:

To investigate the payload diffusion distance of antibody drug conjugates (ADCs) in solid tumors.
To elucidate the interplay between antigen heterogeneity, bystander effects, and ADC delivery.
To inform the design of more effective ADC therapeutics.

Main Methods:

Utilized 3D cell culture and primary human tumor xenograft models.
Tracked fluorescently labeled ADCs and payload via a pharmacodynamic marker (γH2A.X).
Employed TAK-164, an anti-GCC ADC, with its payload DGN549.

Main Results:

The lipophilic payload DGN549 demonstrated penetration beyond the targeted cell layer in tumor spheroids and xenografts.
Observed payload penetration distances aligned with computational model predictions.
Lipophilicity of the payload facilitated moderate tissue penetration, balancing uptake and washout.

Conclusions:

Payload diffusion in ADCs is influenced by lipophilicity, impacting tissue penetration.
Findings contribute to understanding ADC behavior in heterogeneous tumor microenvironments.
Results support the rational design of ADCs with optimized therapeutic effects.