Documents in the NTIS Technical Reports collection are the results of federally funded research. They are directly submitted to or collected by NTIS from Federal agencies for permanent accessibility to industry, academia and the public.  Before purchasing from NTIS, you may want to check for free access from (1) the issuing organization's website; (2) the U.S. Government Printing Office's Federal Digital System website http://www.gpo.gov/fdsys; (3) the federal government Internet portal USA.gov; or (4) a web search conducted using a commercial search engine such as http://www.google.com.
Accession Number ADA570219
Title Targeting Breast Cancer with T Cells Redirected to the Vasculature.
Publication Date Oct 2012
Media Count 11p
Personal Author C. Li G. Coukos N. Scholler N. Scholler
Abstract The overall objective of this project is to develop targeted therapy tools directed against the breast cancer vasculature. We aim to bypass many obstacles in the field by developing a treatment based on the targeting of tumor blood vessels with T cells bearing chimeric immune receptors (CIRs). We have constructed and tested first generation CIR lentiviral vectors targeting hTEM1, which were derived from a panel of scFvs of varying affinity. These constructs signal through CD3 but can be augmented by the addition of costimulatory molecules (CD28 and 4-1BB). In vitro, only T cells bearing the scFv78 CIR were activated upon co-culture with recombinant hTEM1 protein. However, no activation was observed when scFv78 CIR bearing T cells were co- cultured with cells expressing hTEM1 on the surface. Additional strategies, including hinge elongation and the utilization of loadable CIR bearing T cells, also failed to elicit a response against the hTEM1 bearing target cells. We engineered a new yeast-display scFv library from patients with ovarian cancer to isolate a second generation of anti-TEM1 scFvs. We validated a panel of multivalent antibodies for binding to recombinant proteins by ELISA assays. We have generated CIRs against PSMA using scFv (PZ1) and T cells bearing PZ1 and CD28 produce a robust polyfunctional repertoire of cytokines. A tumor vascular mouse model expressing human TEM1 was developed and PET imaging with (124I)-MORAb-004 indicated TEM1-specific accumulation of antibody. We have established optimized HSV-tk as extra safety and tracer for PET imaging.
Keywords Anatomical models
Antibodies
Augmentation
Barriers
Blood vessels
Breast cancer
Cardiovascular system
Cir(Chimeric immune receptor)
Configurations
Disease vectors
Elongation
In vitro analysis
Libraries
Neoplasms
Ovarian cancer
Response
Retroviruses
Safety
T lymphocytes
Targeting
Therapy
Tumor vascular targeting


 
Source Agency Non Paid ADAS
NTIS Subject Category 57A - Anatomy
57S - Physiology
57E - Clinical Medicine
Corporate Author Pennsylvania Univ., Philadelphia.
Document Type Technical report
Title Note Final rept.
NTIS Issue Number 1314
Contract Number W81XWH-10-1-0278

Science and Technology Highlights

See a sampling of the latest scientific, technical and engineering information from NTIS in the NTIS Technical Reports Newsletter

Acrobat Reader Mobile    Acrobat Reader