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

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

Feb 07, 2023 113 likes •503 views

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

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IMPROVED STUDIES ON MALIGNANCIES WITH A NOVEL PROLIFERATION BIOMARKER

  • Thymidine Kinase 1

AROCELL TK 210 ELISA

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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

AGENDA

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PROLIFERATION BIOMARKERS

  • HYPOTHESIS:

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MEASURE WHAT REALLY MATTERS

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HYPOTHESIS:

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MEASURE WHAT REALLY MATTERS

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HYPOTHESIS:

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MEASURE WHAT REALLY MATTERS

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HYPOTHESIS:

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IMMUNOHISTOLOGICAL BIOMARKERS

PROLIFERATION BIOMARKERS

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PROLIFERATION BIOMARKERS

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IMMUNOHISTOLOGICAL BIOMARKERS

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PROLIFERATION BIOMARKERS

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THERE IS A NEED FOR A BIOMARKER THAT:

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SERUM TK1 AS A TUMOR BIOMARKER

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TK1 PROTEIN IN SERUM

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TK1 in serum forms stable complexes of many molecular weights and enzyme activities

All express the TK 210 antigen

TK1 PROTEIN IN SERUM

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MEASURE WHAT REALLY MATTERS

AROCELL TK 210 ELISA

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TK1 IN THE STUDY OF HEMATOLOGICAL MALIGNANCIES

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SERUM TK1 ENZYME ACTIVITY in Hematological Malignancies:

  • Discriminator of disease stage
  • Prognostic information
  • Disease progression
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Serum TK1 Activity and Progression-Free Survival: Chronic Lymphocytic Leukemia

Serum TK1 Correlates with Prognoses

__ TK1 < 7 U/L …. TK1 > 7 U/L p < 0.001

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TK1 IN THE STUDY OF SOLID TUMORS

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  • TK1 IMMUNOHISTOCHEMISTRY:

Expression in solid tumors:

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WHY HAS TK1 NOT BEEN WIDELY STUDIED IN SOLID TUMORS?

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TK1 in serum forms stable complexes of many molecular weights and enzyme activities

All express the TK 210 antigen

TK1 PROTEIN IN SERUM

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But all express the TK 210 antigen

TK1 IS CURRENTLY MEASURED BY ITS ENZYMATIC ACTIVITY Many of the TK1 aggregates in serum from solid tumor subjects are enzymatically inactive

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TK1 ACTIVITY AND MOLECULAR WEIGHT IN HUMAN SERUM

MW of Protein Markers

2 4 6 8 10 12 14 16 18 20 22

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SERUM TK 210 CONCENTRATION / TK1 ENZYME ACTIVITY IN BREAST CANCER

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AUC = 0.90 Sensitivity = 0.50 Specificity = 0.98 AUC = 0.79 Sensitivity = 0.26 Specificity = 0.96

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COMBINING WITH OTHER TUMOR BIOMARKERS

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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

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THYMIDINE KINASE 1 IN DRUG DISCOVERY: AROCELL TK 210 ELISA

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TK1 / TK210 IN CELL* CULTURE EXTRACT

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y = 0.0001x + 0.2327 R² = 0.8999 0.0 0.2 0.4 0.6 0.8 1.0 1.2 2000 4000 6000 8000 10000 ng Cell No.

TK 1 / TK 210 concentration is linear with cell number

*CCRF-CEM, Acute Lymphoblastic Leukemia cell line

Jagarlamudi KK et al. Poster presented at NCRI congress, Liverpool, November 2018

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AROCELL TK 210 ELISA

In-vitro Studies Translational Biomarker Study of Anti-Proliferative Effects In-Vitro

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AROCELL TK 210 ELISA Drug Discovery:

CDK 4/6 inhibitors, Anti-estrogen therapies Directly suppress TK1

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

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AROCELL TK 210 ELISA

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TK1 STABILITY IN SERUM

Storage Time Room temperature 24 hours +4° C 5 days

  • 20°

C 2 months

  • 80°

C Long term storage

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RECENT PUBLICATION

AROCELL TK 210 ELISA

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CONCLUSIONS

THYMIDINE KINASE 1 IN THE STUDY OF MALIGNACIES

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CONCLUSIONS

THYMIDINE KINASE 1 IN THE STUDY OF MALIGNACIES

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MEASURES WHAT REALLY MATTERS

martin.shaw@arocell.com www.arocell.com

AROCELL TK 210 ELISA

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OPEN FOR DISCUSSION

martin.shaw@arocell.com www.arocell.com

AROCELL TK 210 ELISA