Developing functionalized virus like particles for circulating tumor cell detection and enumeration

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Abstract/Contents

Abstract
Circulating Tumor Cells (CTCs) are released from a primary tumor and circulate in the vasculature to form seeds for metastatic colonization at distant locations. There is strong evidence for their use as prognosis markers to indicate the extent of disease progression in cancer patients. For example, the accurate enumeration of CTCs could provide a minimally invasive method to frequently monitor how the cancer responds to therapeutic interventions. Currently there is only one FDA approved CTC assay, CellSearch, but its clinical acceptance has been limited. We seek to develop a point-of-care assay that would detect CTCs based on tumor specific markers. As a model system, we are targeting prostate specific membrane antigen (PSMA), a glycoprotein that is overexpressed on a majority of metastatic prostate cancer cells. The Swartz Lab has developed virus-like particles (VLPs) derived from the Hepatitis B core protein. The VLPs have been stabilized by an engineered disulfide network and display a non-natural amino acid for precise surface augmentation. Using this VLP as a scaffold, nanoparticles (NP) have been developed that can specifically target prostate cancer cells. These NPs are surface functionalized by: a) scFv antibody fragments derived from the PSMA targeting J591 antibody and b) the Gaussia princeps luciferase to provide a luminescent signal. We present work showing feasibility for a point-of-care, highly parallel CTC assay based on these highly engineered VLPs. This technology can facilitate frequent monitoring of cancer patients to ensure that the best possible interventions are employed

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2020; ©2020
Publication date 2020; 2020
Issuance monographic
Language English

Creators/Contributors

Author Mathew, Rinchu
Degree supervisor Swartz, James R
Thesis advisor Swartz, James R
Thesis advisor Dunn, Alexander Robert
Degree committee member Dunn, Alexander Robert
Associated with Stanford University, Department of Chemical Engineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Rinchu Mathew
Note Submitted to the Department of Chemical Engineering
Thesis Thesis Ph.D. Stanford University 2020
Location electronic resource

Access conditions

Copyright
© 2020 by Rinchu Mathew
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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