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:1/20/2017)... ... January 20, 2017 , ... A new partnership between ... they no longer use or need, from clothes to couches to dressers and bicycles. ... and take them to the nearest Goodwill donation center through February 28th. , ...
(Date:1/20/2017)... Miami, Florida (PRWEB) , ... January 20, 2017 , ... ... in head lice cases in families with school-aged children since the holiday season. ... spend the holidays with their families, sharing hugs and taking photos, which is the ...
(Date:1/20/2017)... ... January 20, 2017 , ... ... its sugar-free alternative VW+ 002. The drinks have been produced in collaboration with ... to perform during your workout. , After a successful launch in Sweden last ...
(Date:1/20/2017)... ... 2017 , ... D R Burton Healthcare Products LLC, makers ... in a study indicating superior performance against competitive products in secretion clearance. ... Positive Expiratory Pressure Devices During Simulated Breathing“ was published in the winter issue ...
(Date:1/20/2017)... ... January 20, 2017 , ... “God's Miracle Man: Against All Odds”: an ... of published author, Keith C. A. Tucker, son of Minister Delores Pinnock and a ... by Reverend Mark Hardy , “While sitting up in bed, I felt a pounding ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 19, 2017 Shire plc (LSE: ... U.S. Food and Drug Administration (FDA) has acknowledged receipt ... Application (NDA) for SHP465, a long-acting, triple-bead, mixed amphetamine ... once-daily treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). The FDA is ... 20, 2017, the designated Prescription Drug User Fee Act ...
(Date:1/19/2017)... 19, 2017 Pfizer joins ... Milner Therapeutics Consortium   Major research ... Cambridge   The Milner Therapeutics ... ) as a partner to the Milner Therapeutics Consortium. ... the efficient transfer of materials between industry and academia ...
(Date:1/19/2017)... Florida , January 19, 2017 ... Trump administration appears serious about reducing the FDA,s ... and innovation in the medical drug industry, many ... ahead with new clinical trials and development of ... companies forging ahead with recent developments include:  Moleculin ...
Breaking Medicine Technology: