Validation of the HALO® Platform


HALO Tox Logo
Validation of the HALO® Platform using
the Registry of Cytotoxicity Prediction
Model
 
THE EARLIER POTENTIAL HEMOTOXICITY IS DETECTED IN THE DRUG DISCOVERY AND DEVELOPMENT PIPLINE, THE MORE TIME, COST AND ANIMAL STUDIES CAN BE SAVED, AND THE GREATER THE SAFETY TO THE PATIENT.
 
During validation studies of the HALO® Platform based on the Registry of Cytotoxicity Prediction Model, a large number of compounds (chemicals, anti-inflammatories, anti-cancer drugs etc) were tested on 7 lympho-hematopoietic cell populations (2 stem cell, HPP-SP and CFC-GEMM; 3 hematopoietic, BFU-E, GM-CFC and Mk-CFC; 2 lymphopoietic, T-CFC and B-CFC) simultaneously using fresh primary human and mouse bone marrow target cells, it was found that the response of the lympho-hematopoietic system could be predicted depending on the type and number of cell populations analyzed.

In addition, when the IC50 values of several compounds, determined using the human bone marrow HALO® 7-Population Platform were plotted against the LD50 values (determined by oral administration to rats and mice) of these compounds provided in the Registry of Cytotoxicity, the correlation shown in the diagram below was obtained.
HALO Validation
 
This correlation validates the HALO® Platform as a cytotoxicity assay. However, this correlation also allows HALO® to be used as a predictive test system to estimate initial dosing for in vivo pre-clinical studies and even dosing for human clinical trials. The results presented in the recent article entitled "Validation and Development of a Predictive Paradigm for Hemotoxicology using a Multifunctional Bioluminescence Colony-Forming Proliferation Assay" by I. N. Rich and K.M. Hall published in Toxicological Sciences (87/2: 427-441, 2005) include this information. The article can be downloaded by going to our Downloads Page or clicking on the link. The data shown in Table 3 of this article compares the predicted human clinical dosing of 7 anti-cancer drugs with the dosing used in chemotherapeutic regimens for different types of cancers. It indicates that the HALO® Predictive Hemotoxicity Platform can predict clinical dosing.
 
Particularly important is that most of the drugs tested in this study were not for blood malignancies, but for other types of cancers. Since cancers represent a proliferating population, the HALO® Platform can be used as an important predictive decision-making tool.

HemoGenix® has designed a number of protocols for the HALO® Platform so that it can be used at different stages of drug discovery and development. Because of its flexibility, high-throughput capability and its highly predictive, validated capability, the HALO® Platform is a unique decision-making tool for ADME/Tox screening. It can help save time, cost and animal studies.