Featured Research

from universities, journals, and other organizations

New monoclonal antibody developed that can target proteins inside cancer cells

Date:
March 13, 2013
Source:
Memorial Sloan-Kettering Cancer Center
Summary:
Scientists have created a unique monoclonal antibody that can effectively reach inside a cancer cell.

The ESK1 monoclonal antibody was engineered to recognize WT1 peptides brought to the surface of cancer cells.
Credit: Image courtesy of Memorial Sloan-Kettering Cancer Center

Researchers have discovered a unique monoclonal antibody that can effectively reach inside a cancer cell, a key goal for these important anticancer agents, since most proteins that cause cancer or are associated with cancer are buried inside cancer cells. Scientists from Memorial Sloan-Kettering Cancer Center and Eureka Therapeutics have collaborated to create the new human monoclonal antibody, which targets a protein associated with many types of cancer and is of great interest to cancer researchers.

Unlike other human therapeutic monoclonal antibodies, which can target only proteins that remain on the outside of cancer cells, the new monoclonal antibody, called ESK1, targets a protein that resides on the inside of the cell.

ESK1 is directed at a protein called WT1, which is overexpressed in a range of leukemias and other cancers including myeloma and breast, ovarian, and colorectal cancers. WT1 is a high priority target for cancer drugs because it is an oncogenic protein, meaning that it supports the formation of cancer. In addition, it is found in few healthy cells, so there are less likely to be side effects from drugs that target it.

"This is a new approach for attacking WT1, an important cancer target, with an antibody therapy. This is something that was previously not possible," said David A. Scheinberg, MD, PhD, Chair of the Sloan-Kettering Institute's Molecular Pharmacology and Chemistry Program and an inventor of the antibody. "There has not been a way to make small molecule drugs that can inhibit WT1 function. Our research shows that you can use a monoclonal antibody to recognize a cancer-associated protein inside a cell, and it will destroy the cell."

The first studies of the antibody are showing promise in preclinical research as a treatment for leukemia as reported March 13, 2013, in Science Translational Medicine.

"ESK1 represents a paradigm change for the field of human monoclonal antibody therapeutics," said Cheng Liu, PhD, President and Chief Executive Officer of Eureka Therapeutics. "This research suggests that human antibody therapy is no longer limited to targeting proteins present outside cancer cells, but can now target proteins within the cancer cell itself."

ESK1 was engineered to mimic the functions of a T cell receptor, a key component of the immune system. T cells have a receptor system that is designed to recognize proteins that are inside the cell. As proteins inside the cell get broken down as part of regular cellular processes, molecules known as HLA molecules carry fragments of those proteins -- known as peptides -- to the surface. When T cells recognize certain peptides as abnormal, the T cell kills the diseased cell.

In the current study, the investigators showed that ESK1 alone was able to recognize WT1 peptides and kill cancer cells in the test tube and also in mouse models for two different types of human leukemia. "We were surprised that the antibody worked so well on its own," said Dr. Scheinberg, senior author of the paper. "We had originally expected that we might need to use the antibody as a carrier to deliver a drug or a radioactive therapy to kill the cancer cells, but this was not necessary."

Additional studies must be done in the laboratory before ESK1 is ready to be tested in patients. But the monoclonal antibody was engineered to be fully human, which should speed the time it takes to move the drug into the clinic. Researchers expect that the first clinical trials, for leukemia, could begin in about a year.

The antibody was developed under a collaborative effort between Memorial Sloan-Kettering and Eureka, which have jointly filed for patent protection.

This work was supported by grants from the Leukemia and Lymphoma Society, the National Cancer Institute, the Sloan-Kettering Institute's Experimental Therapeutics Center and Technology Development Fund, the Commonwealth Foundation for Cancer Research, the Tudor and Glades Foundations, the Merker Fund, the Lymphoma Foundation, and the Mesothelioma Applied Research Foundation.


Story Source:

The above story is based on materials provided by Memorial Sloan-Kettering Cancer Center. The original article was written by Julie Grisham. Note: Materials may be edited for content and length.


Journal Reference:

  1. T. Dao, S. Yan, N. Veomett, D. Pankov, L. Zhou, T. Korontsvit, A. Scott, J. Whitten, P. Maslak, E. Casey, T. Tan, H. Liu, V. Zakhaleva, M. Curcio, E. Doubrovina, R. J. O'Reilly, C. Liu, D. A. Scheinberg. Targeting the Intracellular WT1 Oncogene Product with a Therapeutic Human Antibody. Science Translational Medicine, 2013; 5 (176): 176ra33 DOI: 10.1126/scitranslmed.3005661

Cite This Page:

Memorial Sloan-Kettering Cancer Center. "New monoclonal antibody developed that can target proteins inside cancer cells." ScienceDaily. ScienceDaily, 13 March 2013. <www.sciencedaily.com/releases/2013/03/130313160757.htm>.
Memorial Sloan-Kettering Cancer Center. (2013, March 13). New monoclonal antibody developed that can target proteins inside cancer cells. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2013/03/130313160757.htm
Memorial Sloan-Kettering Cancer Center. "New monoclonal antibody developed that can target proteins inside cancer cells." ScienceDaily. www.sciencedaily.com/releases/2013/03/130313160757.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. 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