Studies in drug development and on hematological and solid Tumors with a Thymidine Kinase 1 immunoassay

There are many tumor biomarkers but, they mostly reflect tumor mass or past growth, when what may be more important would be to obtain an indication of future growth and therapy response.

Proliferation biomarkers e.g. KI67, are mostly immunohistological biomarkers which are labor intensive, subjective and only show a small part of the tumor. The ability to measure a proliferation biomarker in an easily available body fluid could reduce this problem and provide new opportunities for studying tumor growth and therapy response. 

Thymidine Kinase 1 (TK1) has the potential to be such as biomarker. 

This presentation will demonstrate how the immunoassay of TK1, using a unique monoclonal antibody directed against the TK 210 epitope (AroCell TK 210 ELISA) can provide new opportunities for the study of tumor growth, therapy response and in-vitro modelling of drug effects.

Thymidine Kinase 1 (TK1) is a key enzyme in DNA synthesis and it is up-regulated in the S phase of cell growth. It is released into the extracellular medium and, eventually, the blood during cell turnover.

TK1 enzyme activity has been used for many years as a biomarker for hematological malignancies but the complexity of the assay, plus the fact that much of serum TK1 is inactive has restricted its use, particularly for solid tumors. However, all TK1 forms express the TK 210 epitope.

In studies on hematological malignancies, the AroCell TK 210 ELISA provides similar information to that of the established enzyme activity assays but in studies on solid tumors, where much of the TK1 is enzymatically inactive, the AroCell TK1 ELISA is more sensitive, without losing specificity.

The AroCell TK 210 ELISA kit can be profitably combined with biomarkers of tissue mass, e.g. CA15-3 increasing diagnostic accuracy.

In in-vitro studies on the effects of anti-cancer drugs, the induction and release of TK1 following drug exposure are similar to those seen in-vivo making the assay of TK1 with the AroCell TK 210 ELISA kit a potentially valuable translational biomarker.

Learning Objectives: 

1. Most current tumor biomarkers provide a linked to tumor mass and/or cell death and are backward looking (past growth).
2. When planning future therapy and making prognoses, biomarkers of current cell growth (proliferation biomarkers) can add valuable additional information.
3. The immunoassay of Thymidine Kinase 1 can be such a biomarker