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

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

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