Bench to Bedside  


A Phase I/II Trial of Cetuximab in Combination With Interleukin-12 Administered to Patients With Unresectable Primary or Recurrent Squamous Cell Carcinoma of the Oropharynx

HYPOTHESIS: Administration of IL-12 will enhance the antitumor activity of cetuximab by activating FcR-positive immune cells that recognize cetuximab-coated tumor cells. The trial combines cetuximab with IL-12 in patients with locally recurrent or unresectable HER1-overexpressing squamous cell carcinoma (SCC) of the oropharynx. Correlative laboratory studies will evaluate the ability of this regimen to activate the innate immune system and relate these events to clinical activity.

RATIONALE: More than 90 percent of oropharyngeal squamous cell carcinomas (SCC) overexpress the epidermal growth factor receptor (EGFR, or HER1). Binding to HER1 by epidermal growth factor (EGF) or transforming growth factor (TGF)-alpha leads to cell cycle progression, reduced cell death (i.e., apoptosis), angiogenesis and metastasis. Tumor HER1 expression correlates with a poor prognosis and resistance to therapy.

Cetuximab is a humanized monoclonal antibody that binds with high affinity to HER1 and shows activity as a single agent in patients with HER1-positive oropharyngeal SCC. When cetuximab binds to HER1 on tumor cells, EGF and TGF-alpha cannot activate the receptor, which reduces proliferation, enhances apoptosis and angiogenesis, inhibits invasiveness and metastasis and down regulates HER1 expression.

This Ohio State-originated clinical trial makes use of the fact that cetuximab and other monoclonal antibody agents possess a binding site in the constant or "Fc" region of the antibody, which is located away from its antigen-binding site. Natural killer cells, monocytes and other innate immune cells bear specialized Fc receptors (FcR) that recognize the antibody's Fc region and enable them to distinguish antibody-coated tumor cells, which they often destroy. Laboratory, preclinical studies and phase I trials indicate that IL-12 can activate FcR-bearing immune cells and enhance their ability to recognize and eliminate antibody-coated tumor cells.

In this trial, we hypothesize that IL-12 will increase the anti-tumor activity of cetuximab in patients with inoperable, HER1-overexpressing oropharyngeal SCC. Our preliminary data strongly indicates that the antitumor activity of IL-12 and cetuximab is dependent on NK cells and their production of IFN-γ, the release of which mobilizes a more effective immune response against cancer cells.

The key objectives of the trial are:
• Identify a safe and tolerable dose of IL-12 in combination with cetuximab.
• Test the ability of IL-12 to enhance response rates to cetuximab in patients who have progressed on a cetuximab-containing regimen.
• Characterize the antitumor mechanism of IL-12 and establish biomarkers that will predict patient responsiveness.

Information gained from this trial should directly apply to other monoclonal antibodies that target HER1 and other oncogenes.

Clinical trial OSU-11010

PI: WILLIAM E. CARSON III, MD, professor of Surgery, associate director
for clinical research and co-leader of the Innate Immunity Program

Phone: 614-293-6306


Eligibility: Patients must be older than 18 years with histologically proven, unresectable, recurrent or metastatic SCC of the oropharynx; one prior systemic therapy is permitted; patients must have progressed on a cetuximab-based regimen or not have responded to it, have an ECOG performance status less than 2, a life expectancy greater than 6 months and normal organ and marrow function.


18  Comments  |  Trackback Url  | 0  Link to this post

Bookmark this post with:        

Links to this post


bidet  commented on  Tuesday, March 06, 2012  1:53 AM 
Thanks for sharing this result.

click here  commented on  Friday, November 16, 2012  12:06 PM 
You made some good points there.

buysupplementsonline  commented on  Saturday, November 17, 2012  10:47 PM 
Interesting and effective for us, good to see this.

endangered species  commented on  Monday, December 24, 2012  5:06 AM 
Digital signage represents a significant investment with the potential for a significant return on investment. Downtime can severely impact that return and turn promising projects into cost disasters. Remote management and recovery is imperative to minimize downtime and reduce costly service calls. Remote power control is the least costly and most flexible way to cover a majority of outages and provides the quickest path to return on investment.  commented on  Wednesday, August 27, 2014  12:09 AM 
Sport betting is the art of predicting sports results by placing a bet or wager on the outcome of the specified sporting event. Sport betting is competitive not only for the bettors but also for the sports books, so shop around for the one that offers the type of bets that you are interested in betting on.  commented on  Wednesday, August 27, 2014  12:10 AM 
We have had a marvellous badminton player who has proven his worth at the recent Asian Games. We have a swimmer who has made a name for herself and even broken a record.  commented on  Wednesday, August 27, 2014  12:10 AM 
If you are not sure which dog breeds are classified as gun dogs, we recommend that you go to one of the Kennel Club web sites such as the American Kennel Club, the United Kingdom Kennel Club or the Canadian Kennel Club.  commented on  Wednesday, August 27, 2014  12:10 AM 
As more and more people begin to become worried about the economy and finding jobs, having a job in the sporting world is great safety job. When I say a great safety job, I mean this is a job where companies are going to be hiring in some way, even though the economy is in a strenuous times.  commented on  Wednesday, August 27, 2014  12:11 AM 
What were they thinking? As of this writing Marion Jones sits in jail for lying about her use of steroids, after having been stripped of her Olympic gold medals for using steroids. Former All Pro Denver Bronco, Lyle Alzado died before his time.  commented on  Wednesday, August 27, 2014  5:49 AM 
Researchers from the Medical University of South Carolina in Charleston analyzed 5,021 participants in the National Health and Nutrition examination Survey 1999-2000 (NHANES 99-00), which was conducted by the National Center for Health Statistics to collect information concerning the health and diet of American men and women.  commented on  Wednesday, August 27, 2014  5:49 AM 
The term "health insurance" is commonly used in the United States to describe any program that helps pay for medical expenses, whether through privately purchased insurance, social insurance or a non-insurance social welfare program funded by the government.  commented on  Wednesday, August 27, 2014  5:50 AM 
Before making a firm decision on a plan that looks attractive consult with a licensed agent about the possibilities that might happen after you submit an application to the insurer. In this article I will explain the possible scenarios that can happen once you apply.

Havells Distribution Board Dealers  commented on  Tuesday, October 07, 2014  2:21 PM 
I found this informative and interesting blog so i think so its very useful and knowledge able.I would like to thank you for the efforts you have made in writing this article.

usammdeals  commented on  Tuesday, October 07, 2014  10:53 PM 
Will, fiquei sabendo que você gosta de Bungee Jumping, manda uma tira de Bungee Jumping ai!

sparxxrx  commented on  Monday, October 20, 2014  5:24 AM 
All of our male enhancement pills are herbal yet effective. Here at SparXXrX® we truly offer the safest, easiest way for you to naturally increase the size of your penis.

psd to html  commented on  Wednesday, November 12, 2014  1:07 AM 
sabendo que você gosta de Bungee Jumping, manda uma tira de Bungee Jumping ai!

Green Smart Living  commented on  Sunday, November 16, 2014  7:25 AM 
the one you mentioned here will be very useful to me! I will post Anine Bing a link to this page on my blog. I am sure my visitors will find that very useful

online marketing  commented on  Tuesday, December 02, 2014  1:00 AM 
significant investment with the potential for a significant return on investment.

Name *:

CAPTCHA Image Validation