Fall 2008
>>From Our Desk To Yours:
MUC16 (CA125): A Cloak and Dagger
UW Gynecologic Approach to Immune Evasion
Oncology Team by Manish Patankar, PhD - Assistant Professor, Department of OB/GYN
Joseph P. Connor, MD
Gynecologic Oncologist
A.C. Evans, MD, PhD
C ancer, as we all know, can be a
tricky and evasive opponent.
Ovarian cancer is no exception, and
Gynecologic Oncologist utilizes a huge molecule, MUC16, to
perform two very important tasks involved
Ellen M. Hartenbach, MD in escaping the immune system: providing a
Gynecologic Oncologist cloak to mask the tumor cells from
immune recognition and secreting the same
David M. Kushner, MD molecule to bind to and switch off immune Patankar-Connor Research Group
Gynecologic Oncologist cells (the dagger).The MUC16 molecule Back left to right- Mildred Felder, Jennifer Belisle,
carries a repeating peptide epitope that is Jennifer Gubbels, Manish Patankar, Joseph Connor,
Laurel W. Rice, MD more commonly known by clinicians as and David Engle. Front left to right- Chanel Tyler,
Gynecologic Oncologist the ovarian tumor marker, CA125. Our lab Sarah Petrie, and Arvinder Kapur.
has determined that the importance of
Stephen L. Rose, MD CA125 (MUC16) is not merely confined to The tumor cells also release MUC16 in
Gynecologic Oncologist monitoring the progression of epithelial the peritoneal environment and the blood
ovarian cancer. Instead, MUC16 promotes stream.The released MUC16 (the dagger)
Howard H. Bailey, MD the progression of ovarian tumors using this
Medical Oncologist
specifically binds and inhibits the function
cloak and dagger approach. of some immune cells and renders them
Kristin A. Bradley, MD non-responsive to the cancer. For efficient
The MUC16 molecule is composed of over immunologic control of the cancer it will
Radiation Oncologist
24,000 amino acids, is decorated with be necessary to devise methods to
carbohydrate chains, and has an estimated circumvent or overcome the profound
Manish S. Patankar, PhD
mass of 3-5 million Da. Ovarian cancer immunesuppression mediated by MUC16
Research Scientist
tumor cells are covered with this enormous and other tumor derived factors.
molecule (see Figure). Research conducted
Joanne K. Rash, PA-C
Physician Assistant
in our laboratory has confirmed that for
metastasis the ovarian tumor cells utilize
Lori A. Seaborne, PA-C the MUC16 cloak present on their cell
Physician Assistant surface to latch-on to the abdominal wall.
Margaret R. Straub, PA-C The presence of this MUC16 cloak,
Physician Assistant however, acts as a barrier that prevents
immune cells from efficiently recognizing
and killing the ovarian cancer cells. MUC16
is therefore used as a primal line of defense
against immunologic surveillance.
Our on-going work is focused on strategies Fluorescent image of an ovarian cancer cell.
that can be utilized to promote the immune The MUC16 molecules present on the entire cell surface
are shown in green.
cells to identify the tumor even in the
presence of such an obfuscating
MUC16 cloak.
>> Our Feature Protocol : Translational Research
Clinical Study of Muc16 (CA125):
A new MUC16 (CA125) based test for monitoring ovarian cancer recurrence
An increase in serum CA125 the laboratory and will be assayed for
levels from a nadir value indicates
recurrence of epithelial ovarian cancer.
serum CA125 levels. In addition the
immune cells will be isolated and
>> Protocol Eligibility*
While studying the biological MUC16 bound to these cells will be Key eligibility criteria*:
properties of MUC16, our lab quantified using a standard laboratory • Presumed advanced ovarian cancer
determined that specific subsets of technique known as flow cytometry. (presence of pelvic mass, elevated
immune cells derived from ovarian MUC16 levels on the immune cells will CA125 and/or ascites)
cancer patients carried this molecule be correlated with the recurrence of • Follow-up care at UW, or willingness to
on their cell surface. Using sensitive ovarian cancer in the patients.
detection methods we determined that The healthy donor samples will be come to UW for blood draws
MUC16 could be found attached to the analyzed to determine the baseline • No history of another invasive
immune cells even when the serum levels of immune cell bound MUC16 in malignancy
MUC16 levels, measured by the the population. • Age 18 or over
conventional CA125 assay, are low or
even undetectable.This led us to These studies are approved by the *select eligibility
hypothesize that measuring the Institutional Review Board (IRB) of
immune cell bound MUC16 may be the University of Wisconsin-Madison.
a better predictor of ovarian cancer Patients and healthy donors will be
recurrence than the serum CA125 well informed about the objectives
assay. We are now recruiting healthy of the study and will sign a consent
volunteers and ovarian cancer patients form prior to participation. Since only
to prove this hypothesis. These studies a small volume of blood will be drawn
are funded by a two-year grant from the from the healthy donors and cancer
Medical Education and Research patients by venipuncture, the risks for
Committee (MERC), an intramural participating in the study are minimal.
funding agency.
As a part of this study we will obtain
10-20 ml blood samples from healthy
donors and ovarian cancer patients.
Image of an ovarian cancer cell (red cell on top)
Blood samples from the cancer patients
being attacked by an immune cell (green cell at the
will be drawn prior to cytoreductive bottom). The blue stain shows the nucleus of both
therapy, and during the three follow-up the cancer cell and the immune cell. This picture
visits following chemotherapy. was taken by Jenny Gubbels, a graduate
The blood samples will be processed in student in the Patankar lab.
>> Introducing New Team Members
Drs. Margaret Heather Einstein and Ahmed Al-Niaimi
have joined our team as our first Fellows in
Gynecologic Oncology at the University of Wisconsin.
The fellowship is a three-year training program
and one of forty throughout the United States.
Margaret Heather Einstein, M.D. Ahmed Al-Niaimi, M.D.
Fellow in Gynecologic Oncology Fellow in Gynecologic Oncology
>> Our Current Protocols A complete listing of all clinical trials at the UW Carbone Cancer Center
is also available on our website, www.cancer.wisc.edu.
Ovarian
GOG 126R A phase II Evaluation of Abraxane® in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian,
Fallopian Tube, or Primary Peritoneal Cancer
GOG 212 A Randomized Phase III Trial of Maintenance Chemotherapy Comparing Single Agent Paclitaxel or Xyotax Versus
No Treatment Until Documented Relapse in Women with Advanced Ovarian or Primary Peritoneal Cancer
GOG 213 A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel Alone or in Combination with Bevacizumab
Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian,
Peritoneal Primary and Fallopian Tube Cancer
GOG 218 A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent Bevacizumab
In Women with Newly Diagnosed, Previously Untreated, Advanced Stage Epithelial Ovarian and Peritoneal Cancer
CO 07702 A Phase III Randomized, Blinded, Placebo-controlled Trial of Carboplatin and Gemcitabine plus Bevacizumab in Patients
with Platinum-Sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma
GOG 214 A Phase II Double Blind Randomized Trial Evaluating the Biologic Effect of Levonorgestral on the Ovarian Epithelium
in Women at High Risk for Ovarian Cancer
Uterine
GOG 209 A Randomized Phase III Trial of Doxorubicin/Cisplatin/Paclitaxel and G-CSF versus Carboplatin/Paclitaxel in
Patients with Stage III & IV or Recurrent Endometrial Cancer
GOG 87M A Phase II Evaluation of Trabectedin (Yondelis®) in the Treatment of Advanced, Persistent or
Recurrent Uterine Leiomyosarcoma
GOG 232C A Phase II Evaluation of Paclitaxel, Carboplatin, and BSI-201 in the Treatment of Advanced, Persistent, or
Recurrent Uterine Carcinosarcoma
GOG 238 A Randomized Trial of Pelvic Irradiation With or Without Concurrent Weekly Cisplatin in Patients with Pelvic-Only
Recurrence of Carcinoma of the Uterine Corpus
CC 07703 Quality of Life and Sexual Functioning in Endometrial Cancer Survivors
Cervical
GOG 9918 A Phase I Trial of Tailored Radiation Therapy with Concomitant Cetuximab and Cisplatin in the Treatment
of Patients with Cervical Cancer
RTOG 0418 A Phase II Study of Intensity Modulated Radiation Therapy (IMRT) to the Pelvis +/- Chemotherapy for
Post-operative Patients with Cervical Carcinoma
Vulvar
GOG 173 Intraoperative Lymphatic Mapping and Sentinel Node Identification in Patients with Squamous Cell
Carcinoma of the Vulva
>> For more information about these clinical trials >> UW Gynecologic Oncology Research Staff:
at the UW Carbone Cancer Center, contact Cancer • Sarah L. Stewart, Research Program Manager
Connect, (800) 622-8922 or (608) 262-5223 in the • Angela M. Marchant, Clinical Research Associate
Madison area. • Katy A. Mijal, Clinical Research Associate
• Our current List of Open Protocol
Muc16 (CA125)
Translational Research: Clinical Study of
• Feature Protocol:
by Manish Patankar, PhD Learn More About UW Gynecologic Oncology
Approach to Immune Evasion” We Can Save Lives
• “MUC16 (CA125): A Cloak and Dagger
>> Inside This Issue Together
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• Recently accumulated research shows that 600 Highland Ave., K4/658
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• Common side effects of cervical cancer
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• Common side effects of ovarian cancer
include bloating, pelvic or abdominal pain,
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