IMPROVED STUDIES ON MALIGNANCIES WITH A NOVEL PROLIFERATION - PowerPoint PPT Presentation

IMPROVED STUDIES ON MALIGNANCIES WITH A NOVEL PROLIFERATION BIOMARKER - Thymidine Kinase 1 AROCELL TK 210 ELISA 1

AGENDA 1 Proliferation Biomarkers 2 Thymidine Kinase 1 as a Tumor Biomarker 3 Thymidine Kinase 1 in the Study of Hematological Malignancies 4 Thymidine Kinase 1 in the Study of Solid Tumors 5 Thymidine Kinase 1 in In-Vitro Drug Discovery 6 Immunoassay of TK1 – AroCell TK 210 ELISA 7 Summary and Discussion 2

PROLIFERATION BIOMARKERS HYPOTHESIS: • • • • • 3

MEASURE WHAT REALLY MATTERS HYPOTHESIS: • • • 4

MEASURE WHAT REALLY MATTERS HYPOTHESIS: • • • • 5

MEASURE WHAT REALLY MATTERS HYPOTHESIS: • • • 6

PROLIFERATION BIOMARKERS IMMUNOHISTOLOGICAL BIOMARKERS 7

PROLIFERATION BIOMARKERS IMMUNOHISTOLOGICAL BIOMARKERS • • • 8

PROLIFERATION BIOMARKERS THERE IS A NEED FOR A BIOMARKER THAT: • • • 9

SERUM TK1 AS A TUMOR BIOMARKER • • • 10

TK1 PROTEIN IN SERUM • • • • 11

TK1 PROTEIN IN SERUM TK1 in serum forms stable complexes of many molecular weights and enzyme activities All express the TK 210 antigen 12

AROCELL TK 210 ELISA MEASURE WHAT REALLY MATTERS • • 13

TK1 IN THE STUDY OF HEMATOLOGICAL MALIGNANCIES 14

SERUM TK1 ENZYME ACTIVITY in Hematological Malignancies: • Discriminator of disease stage • Prognostic information • Disease progression 15

Serum TK1 Correlates with Prognoses __ TK1 < 7 U/L …. TK1 > 7 U/L p < 0.001 Serum TK1 Activity and Progression-Free Survival: Chronic Lymphocytic Leukemia 16

TK1 IN THE STUDY OF SOLID TUMORS

TK1 IMMUNOHISTOCHEMISTRY: Expression in solid tumors: • • • • • • 18

WHY HAS TK1 NOT BEEN WIDELY STUDIED IN SOLID TUMORS? 19

TK1 PROTEIN IN SERUM TK1 in serum forms stable complexes of many molecular weights and enzyme activities All express the TK 210 antigen 20

TK1 IS CURRENTLY MEASURED BY ITS ENZYMATIC ACTIVITY Many of the TK1 aggregates in serum from solid tumor subjects are enzymatically inactive But all express the TK 210 antigen 21

TK1 ACTIVITY AND MOLECULAR WEIGHT IN HUMAN SERUM MW of Protein Markers 2 4 6 8 10 12 14 16 18 20 22 22

SERUM TK 210 CONCENTRATION / TK1 ENZYME ACTIVITY IN BREAST CANCER AUC = 0.79 AUC = 0.90 Sensitivity = 0.26 Sensitivity = 0.50 Specificity = 0.96 Specificity = 0.98 23

COMBINING WITH OTHER TUMOR BIOMARKERS 24

AROCELL TK 210 ELISA Solid tumors Improved Sensitivity Compared with TK1 Activity Assays Improved Discrimination between Healthy and Subjects with Malignancies Positive Synergy with other Biomarkers 25

THYMIDINE KINASE 1 IN DRUG DISCOVERY: AROCELL TK 210 ELISA 26

TK1 / TK210 IN CELL* CULTURE EXTRACT 1.2 1.0 0.8 *CCRF-CEM, Acute ng 0.6 Lymphoblastic y = 0.0001x + 0.2327 Leukemia cell line R² = 0.8999 0.4 0.2 0.0 0 2000 4000 6000 8000 10000 Cell No. TK 1 / TK 210 concentration is linear with cell number Jagarlamudi KK et al . Poster presented at NCRI congress, Liverpool, November 2018 27

AROCELL TK 210 ELISA In-vitro Studies Translational Biomarker Study of Anti-Proliferative Effects In-Vitro 28

AROCELL TK 210 ELISA Drug Discovery: CDK 4/6 inhibitors, Anti-estrogen therapies Directly suppress TK1 29

AROCELL TK 210 ELISA A UNIQUE BIOMARKER FOR CELLULAR PROLIFERATION Assay Procedure 30

AROCELL TK 210 ELISA • • • • 31

TK1 STABILITY IN SERUM Storage Time Room 24 hours temperature +4 ° C 5 days 2 months -20 ° C Long term storage -80 ° C 32

AROCELL TK 210 ELISA RECENT PUBLICATION 33

THYMIDINE KINASE 1 IN THE STUDY OF MALIGNACIES CONCLUSIONS • • • • • 34

THYMIDINE KINASE 1 IN THE STUDY OF MALIGNACIES CONCLUSIONS • • • • 35

AROCELL TK 210 ELISA MEASURES WHAT REALLY MATTERS martin.shaw@arocell.com www.arocell.com 36

AROCELL TK 210 ELISA • • OPEN FOR DISCUSSION martin.shaw@arocell.com www.arocell.com