Featured Research

from universities, journals, and other organizations

Engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice

Date:
August 8, 2011
Source:
University of Pennsylvania School of Medicine
Summary:
Medical researchers have shown for the first time that engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice.

In a recent issue of Cancer Research, Daniel J. Powell, Jr., PhD, a research assistant professor of Pathology and Laboratory Medicine and Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania, showed for the first time that engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice. Ovarian cancer is the most lethal reproductive cancer for women, with one-fifth of women diagnosed with advanced disease surviving five years. Nearly all ovarian cancers (90%) are characterized by their expression of a distinct cell-surface protein called alpha-folate receptor, which can be a target for engineered T cells.

In a past clinical study, first generation engineered T cells did not shrink tumors in women with ovarian cancer because the T cells did not persist in the patients. The new second generation technology developed in the current study overcomes the limitations of the first generation approach. Here, second generation T cells shrank tumors; whereas, T cells engineered using first generation technology did not.

The alpha-folate receptor is expressed on the surface of ovarian cancer cells and has a high affinity for folic acid, a vitamin which helps "feed" the cancer cells, and represents an "Achilles' Heel" for cancer researchers to target.

"We anticipate the opening of a genetically modified T cell clinical trial in the next few months for women with recurrent ovarian cancer," says Powell. "Targeting the alpha-folate receptor is an opportunity for widespread clinical application."

Until now, human T cells engineered to express an antibody fragment specific for the alpha-folate receptor protein have shown anti-tumor activity against epithelial cancers in the lab, but not in the clinic due to their inability to persist and home to tumors in the human body. The modified T cells used in this study express an engineered fusion protein -- called a chimeric antigen receptor -- that combines the specificity of an antibody with the T cell signaling portions from two different proteins that stimulate the immune system to recognize ovarian cancer cells. These added signaling protein pieces give the engineered T cells the extra survival signals they need to do their job.

Two Birds, One Stone T Cells

The double-barreled cells are engineered to multiply, survive, recognize, and kill ovarian tumors. The modified T cells are expanded for two weeks in the lab, and then tested for reactivity by exposing them to human ovarian cancer cells to see if they destroy the cancer cells. Researchers also test for effectiveness by measuring cytokine production by the T cells, a sign of inflammation produced by the engineered T cells when killing cancer cells.

The new second generation engineered cells were successful in many ways. They were resistant to cancer-induced cell death: Fewer new T cells died when exposed to cancer cells, compared to the older technology. The new T cells also multiply better and survive; therefore their numbers increase over time in test-tube experiments and in the mouse model.

A clinical trial using these T cells is pending with George Coukos, MD, Director of the Ovarian Cancer Research Center at Penn and the trial's principal investigator. Penn is the only study site identified to date. Investigators aim to recruit up to 21 patients with advanced recurrent ovarian cancer whose tumors express the alpha-folate receptor.

"This technology represents a promising advancement for the treatment of women with ovarian cancer," Powell says, "But we will continue to work around the clock to improve this approach using other costimulatory portions and antibody-like proteins to make this the most powerful and safe approach for the treatment of the greatest number of women with this horrible disease."


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. D.-G. Song, Q. Ye, C. Carpenito, M. Poussin, L.-P. Wang, C. Ji, M. Figini, C. H. June, G. Coukos, D. J. Powell. In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB). Cancer Research, 2011; 71 (13): 4617 DOI: 10.1158/0008-5472.CAN-11-0422

Cite This Page:

University of Pennsylvania School of Medicine. "Engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice." ScienceDaily. ScienceDaily, 8 August 2011. <www.sciencedaily.com/releases/2011/08/110808115412.htm>.
University of Pennsylvania School of Medicine. (2011, August 8). Engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/08/110808115412.htm
University of Pennsylvania School of Medicine. "Engineered human T cells can eradicate deadly human ovarian cancer in immune-deficient mice." ScienceDaily. www.sciencedaily.com/releases/2011/08/110808115412.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins