Navigation Links
New universal platform for cancer immunotherapy developed by Penn-led team
Date:3/5/2012

PHILADELPHIA - Researchers from the Perelman School of Medicine at the University of Pennsylvania report this month in Cancer Research a universal approach to personalized cancer therapy based on T cells. It is the first time a system for making an adaptable, engineered T-cell to attack specific tumor types has been proposed, depending on which abnormal proteins, called antigens, are expressed by individual patients' tumor cells.

For now, the system is being refined in experiments using healthy donor T cells and animal models of human cancer, with the aim to introduce the personalized cells into patients in the future, explains senior author Daniel J. Powell Jr., Ph.D., a research assistant professor of Pathology and Laboratory Medicine with Penn's Ovarian Cancer Research Center.

Tumor antigens are potential targets of an immune response, and identifying which antigens a patient's tumor cells express would be helpful in designing cancer therapy for that individual. Any mutated protein produced in a tumor cell can act as a tumor antigen. Many tumor cells have surface proteins that are inappropriately expressed for the cell type, or are only normally present during embryonic development. Still other tumor cells display cell surface proteins that are rare or absent on the surfaces of healthy cells and are responsible for activating molecular pathways that cause uncontrolled replication of cells. In most cancers, not all patients have tumor cells that express the exact same antigen, and sometimes tumor cells from a single patient can express different antigens. Because of this complexity, it is important to properly choose which antigen to target with cancer therapy.

T cells engineered to express an engineered antigen, called a chimeric antigen receptor (CAR), offer an attractive strategy for targeting antigens and treating cancer, says Powell. CARs are engineered receptors that graft, for example, the portion of a tumor-specific antibody onto an immune cell. This allows the patients' T cells to recognize tumor antigens and kill their tumor cells.

For therapy, a large number of tumor-specific, cancer-fighting CAR T cells can be generated in a specialized lab using patients' own T cells, which are then infused back into them. This approach has shown promising results in patients whose tumors all express the same antigen.

Despite these encouraging findings, currently made CARs have a fixed antigen specificity, which means only one type of tumor antigen can be targeted at a time. Tumor cells that lack that selected antigen can then escape recognition by immune cells and replicate, limiting what might otherwise have been an effective therapy if multiple tumor antigens had been targeted. For this reason, the team sought to make a more generalized receptor framework that is able to produce T cells capable of targeting large panels of known tumor antigens.

To that end, the team developed a new platform from which they could eventually target a variety of tumor antigens, either simultaneously or sequentially. So far, they have engineered T cells against the antigens mesothelin, present on several tumor cell types; epCAM, present on epithelial cell cancers; alpha folate, present on ovarian cancer cells; and, more recently, CD19 on lymphoma cells.

The universal immune receptor recognizes molecules attached to tumor antigens on the surface of tumor cells. When this happens, the T cells produce inflammatory response proteins called cytokines and pore-forming proteins. Those proteins cause the release of enzymes through those pores into tumor cells, thereby killing them.

The new engineered T cells described in the Cancer Research paper recognize and bind exclusively to cancer cells pre-targeted with biotin-labeled molecules, such as antibodies. Biotin is a B complex vitamin necessary for cell growth that can be bound by a molecule called avidin, which is contained in the universal immune receptor. Since nearly any molecule can be biotin labeled, the number of antigens that can be targeted by T cells carrying the biotin-binding immune receptor is nearly infinite. The versatility afforded by this biotin-binding receptor permitted the targeting of a combination of distinct antigens all at once, and even one after another, notes Powell.

The findings demonstrate that a universal T cell can significantly extend conventional CAR approaches, allowing the team to generate T cells of unlimited antigen specificity. This process is geared to make T cell therapy more available to patients and to improve the effectiveness of T-cell immunotherapies for cancer.

First author post-doctoral fellow Katarzyna Urbanska, Ph.D. continues optimization of the universal receptor approach by looking for different ways to improve the interaction of T cells with tumor cells, and how to better direct the T cells and the biotin-labeled molecules to tumor cells in the body.

In the future, Powell and colleagues predict a highly personalized platform for cancer therapy that begins when patient tumors are analyzed for their expression of specific antigens at the Department Pathology and Laboratory Medicine's new Center for Personalized Diagnostics. When the antigens expressed by a patient's tumor cells are determined, their T cells will be engineered to express the universal immune receptor, which will be given back to them in combination with biotin-labeled molecules to attach to patients' tumor antigens for an individualized tumor attack.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Study finds shifting disease burden following universal Hib vaccination
2. Researchers Closer to Developing Universal Meningitis B Vaccine
3. Universal flu vaccine clinical trials show promise
4. Brazils health care system vastly expands coverage, but universality, equity remain elusive
5. Universal screening programs can uncover abuse, study finds
6. Internists remind physicians about universal ethical principles
7. Universal flu vaccine study yields success in mice
8. Universal Flu Vaccine Shows Promise in Early Trial
9. Pandemic flu strain could point way to universal vaccine
10. Universal standards proposed for prescription container labels to help reduce medication misuse
11. World Health Report 2010 balanced but incomplete account of how to achieve universal health coverage
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New universal platform for cancer immunotherapy developed by Penn-led team
(Date:4/28/2016)... ... ... Card reminds us that May is National Stroke Awareness Month. According to the Centers ... in the United States; someone has one every 40 seconds. Annually, almost 800,000 strokes ... old. A stroke is when blood flow to the brain is blocked or when ...
(Date:4/28/2016)... ... April 28, 2016 , ... Point ... miniature microphones and headsets announced today that the US Patent Office has approved ... into a structure. This innovative design creates a lightweight and modular audio headset ...
(Date:4/28/2016)... ... April 28, 2016 , ... Accreditation Commission for ... Pharmacy Association (COPA) to develop a comprehensive Specialty Pharmacy Accreditation with Distinction in ... accreditation distinction. ACHC provides a wide range of pharmacy accreditation services that assess ...
(Date:4/28/2016)... ... April 28, 2016 , ... Starting today, households ... mail from USA Medical Prescription Assistance Program. They are customized to reflect the ... package will include a ready-to-use, state-themed card and, in the near future, material ...
(Date:4/28/2016)... (PRWEB) , ... April 28, 2016 , ... For the ... means getting smarter about an important part of overall well-being: mental health. Now, a ... do to promote healthy aging and “cognitive vitality,” which can include everything from honing ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... , April 28, 2016  While Abbott,s ... complement the company,s valve repair and stent business, ... also places Abbott more firmly into patient monitoring.  ... the fastest growing device areas, with double-digit growth ... recent report,  Advanced Remote Patient Monitoring ...
(Date:4/28/2016)... Research and Markets has announced the addition ... report to their offering.      (Logo: ... plastic surgery products market is expected to grow at ... ,The growing adoption of laser in aesthetics is another ... Lasers are used to treat a broad range of ...
(Date:4/28/2016)... April 28, 2016  Marking its one year ... and ovarian cancer risk test, Color Genomics ... genes that highly impact the most common hereditary ... the Color Test analyzes hereditary cancer risks for ... uterine cancers. The Color Test is physician ordered ...
Breaking Medicine Technology: