A NOVEL ANTIBODY FOR THE DETECTION AND TREATMENT OF PANCREATIC DUCTAL ADENOCARCINOMA

1 online resource (106 pages) : PDF

2017

University of North Carolina at Charlotte

Pancreatic ductal adenocarcinoma (PDA) remains the most aggressive cancer with a 5-year survival rate below 10%. Two of the major contributors to this dismal prognosis are late-stage diagnosis and limited treatment options. Common symptoms of PDA like weight loss, abdominal pains, and jaundice do not appear until the cancer has progressed to late stage and the tumor is of significant size. Surgery and systemic delivery of chemotherapies is the standard treatment for patients, but the associated side effects are severe and the overall survival rate remains unchanged. Therefore early detection (Chapter 2) and targeted drug delivery (Chapter 3) in PDA is highly desirable. Mucin 1 (MUC1) is a tumor-associated antigen (tMUC1) expressed on 80% of human PDA. Here I report the targeting capabilities of TAB004, a tMUC1 specific antibody, for diagnosing and treatment purposes using a fluorophore bound antibody and a TAB004-conjugated PEGylated PLGA (poly lactic-co-glycolic acid) nanoparticle that is loaded with a paclitaxel (PTX). In orthotopic immunocompetent mice, I show that TAB004 specifically targets the tumor without significant accumulation in other organs. Conjugating TAB004 to the surface of PLGA Nanoparticles (T-NPs) significantly increased their internalization into PDA cells as well as their cytolysis of PDA cells when compared to the non-conjugated PLGA-NPs. In vivo, the T-NPs showed dramatically increased accumulation within the pancreatic tumor when compared to the non-conjugated PLGA NPs. The data suggests that TAB004 is a promising antibody to deliver imaging agents and treatments directly to the pancreatic tumor microenvironment, thus improving detection and treatment of PDA.

doctoral dissertations

Biology
Oncology

Ph.D.

MUCL
Mucin 1
Nanoparticles
Pancreatic Cancer
PLGA
Targeted Therapy

Biology

Mukherjee, Pinku

Dreau, Didier
Ogle, Craig
Richardson, Christine
Yan, Shan

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2017.

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Wu_uncc_0694D_11527

http://hdl.handle.net/20.500.13093/etd:491