Drug discovery and development

Thymidine Kinase 1 (TK1) is a sensitive cell proliferation and disruption biomarker that has been used to study hematological malignancies and solid tumors1. Measurement of proliferation, or progression and remission of tumor growth is important early in the drug development process and can aid in the selection of drug candidates. Only few cell proliferation biomarkers are suitable for large-scale in vitro studies. TK1 as a biomarker using AroCell TK 210 ELISA, opens the opportunity to monitor the efficacy and dose response of drugs or drug candidates in drug discovery and development.

In vitro Cell culture studies

In a recent investigation2, a lymphoblast cell line (CCRF-CEM TK+) and MDA MB-231 cells were exposed to a range of doses of doxorubicin and the TK1 protein levels were then determined in cell extracts and culture supernatants using AroCell TK 210 ELISA.

Clear dose responses were determined in both the cell extracts and culture supernatants with an increase in cellular TK1 when cells were exposed to low concentrations of doxorubicin (1 μM), and the release of TK1 into the cell culture media when higher concentrations of doxorubicin (10 μM) were used to treat the cells. Changes in intra- and extracellular TK1 levels, apparently related to the mechanism of cytotoxicity of anti-cancer agents, could be detected using as few as 800 cells and in only 24 h of incubation. In vitro measurements of TK1 in cell cultures using AroCell TK 210 ELISA provides an opportunity for monitoring the efficacy of drugs in preclinical drug discovery and development using TK1 as proliferation biomarker2.

AroCell TK 210 ELISA is CE-marked under the IVD directive and is well-suited for studying dose response from and efficacy of drugs and drug candidates in vitro, as a translational biomarker and as a proliferation and cell disruption oncology  biomarker in human clinical trials. The ability to perform studies using a very small number of cells reduces costs and makes the assay suitable for high-throughput screening in drug discovery.

Xenograft animal models

Potential therapeutic compounds are often studied using tumor xenografts in immunodeficient mice. TK1 activity assays will measure TK1 derived from both the human graft and the host. However, the human TK 210 antigen differs from that in mice, enabling better discrimination of the effects of the test substance on the tumor graft than using TK1 activity assays.

  1. Jagarlamudi K.K. and Shaw, M. Thymidine Kinase 1 as a tumor biomarker: technical advances offer new potential to an old biomarker. Biomark Med. 2018 Sep;12(9):1035-1048. Epub 2018 Jul 24, 2 Aug.
    https://www.ncbi.nlm.nih.gov/pubmed/30039979
  1. Jagarlamudi K.K., Wang, L. and Eriksson, S. Doxorubicin effects on leukemia and breast cancer cells in culture on the TK1 protein levels using AroCell TK 210 ELISA: a tool for drug development. Nucleosides Nucleotides Nucleic Acids. 2018 Dec 6:1-8.
    https://www.ncbi.nlm.nih.gov/pubmed/30520339