CA125: More than Just a Biomarker

Manish S. Patankar, PhDUniversity of Wisconsin-Madison

Department of OB/GYNDivision of Gynecologic Oncology

• What is CA125?

• Why is CA125 detected in the blood of cancer patients?

• Why do ovarian cancer cells produce CA125?

Ovarian Cancer Cell Under an Electron Microscope

27-30 micrometer

How small are cancer cells?

Diameter of a penny is 19.05 millimeter or 19,050 micrometer

The diameter of a cancer cell is approximately 1/700th-1/600th of a penny

TumorCancer cell Time

Diagnosis and treatment

Research at University of Wisconsin-Madison

• Understanding the biological role of CA125 in ovarian cancer

• Developing immunotherapeutic agents that target ovarian cancer

• Developing novel therapeutic agents that can inhibit the growth of cancer cells

Using Natural Killer Cells (NK) to target ovarian cancer

Cancer cell

NK

NK

Cell Death

Cancer cell

NK

NK cells attack cancer cells

Boosting the anti-cancer activity of NK cells

Cancer cell

NK

NK

• huKS-IL2

• Resveratrol

Boosting the anti-cancer activity of NK cells

Cancer cell

NK

• huKS-IL2: Increases the ability of NK cells to bind to cancer cells

• Resveratrol activates NK cells

Cell Death

• Conjugated Linoleic acid (CLA)

• A constituent of milk and red meat

• CLA inhibits growth of ovarian cancer cells when tested under experimental conditions

New therapeutic agents

Research at University of Wisconsin-Madison

• Understanding the biological role of CA125 in ovarian cancer

• Developing immunotherapeutic agents that target ovarian cancer

• Developing novel therapeutic agents that can inhibit the growth of cancer cells

What is CA125?CA125 is a tiny part of a very large molecule called MUC16

Ovarian Cancer cell

CA125

CA125

CA125

MUC16

MUC16 Under an Electron Microscope

Mol. Wt= 3-10 million Da

1-2 mm in length

Courtesy of Dr. John Sheehan, U. North Carolina

Mo

lecu

lar

size

Hemoglobin Antibody MUC16

Why is CA125 Detected in the Blood?

Ovarian Cancer cell

CA125

CA125

CA125

Why is CA125 Detected in the Blood?

Ovarian Cancer cell

CA125

CA125

CA125

Blood

Serum CA125 Assay

CA125

• CA125 is not useful for early detection of ovarian cancer

• Used only for follow-up

• Study from an European trial (MRC OV05/EORTC 55955) suggest that early treatment of recurrent cancer determined by rise in CA125 does not result in benefit in survival of patients

Ovarian Cancer cell

CA125

CA125

CA125

Importance of MUC16 (CA125) in Ovarian Cancer

Cell Death

Ovarian Cancer cell

CA125

CA125

CA125

Importance of MUC16 (CA125) in Ovarian Cancer

No Cell Death

Ovarian Cancer cell

Importance of MUC16 (CA125) in Ovarian Cancer

Cell Death

NK

NK

MUC16 Protects Ovarian Cancer Cells from NK cells

Ovarian Cancer

Ovarian Cancer

NK

NK

MUC16low MUC16medium MUC16high

NK cells selectively target csMUC16low cells

csMUC16low csMUC16medium csMUC16high0

10

20

30

40

Nu

mb

er o

f co

nju

gat

es

MUC16 binds to NK cells

NK

Ovarian Cancer cell

NK

Blood vessel

Loss of MUC16 Increases Survival of Ovarian Cancer Bearing Mice

0 50 100 150 200 250 3000

102030405060708090

100110

MUC16 neg -OVCMUC16 pos -OVC

Days

Per

cen

t su

rviv

al

Introduce agents that inhibit production of MUC16 (CA125)

OvarianTumor

Decrease in MUC16 (CA125) will

• Induce cancer cell death

• Disarm the cells and allow targeting by NK cells

Introduce NK cells to target tumors

Our Team

• Dr. Arvinder Kapur, Dr. Rebecca Whelan, Mildred Felder, Kai Ludwig, Soma Banerjee, and Yang Liu

• Drs. David Kushner, Ellen Hartenbach, Laurel Rice, Steve Rose, Ahmed Al-Niami

• Drs. Nonyem Onujiogu, Mian Shahzad, Shitanshu Uppal

• Drs. Paul Sondel, Paul Campagnola, Pamela Kreeger, Arthur Polans, and Irwin Goldman