Publication Date

Spring 2021

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Engineering

Advisor

Folarin F. Erogbogbo

Keywords

cancer immunotherapy, CAR T cell therapy, chemokine receptors, immunotherapy, ovarian cancer

Subject Areas

Biomedical engineering; Immunology

Abstract

The proposed work aims to overcome the economical and feasibility-related limitations of the chimeric antigen receptor therapies by developing an artificial cell signaling pathway whose design transforms K562 cells into in vivo living vectors to synthesize therapeutic proteins upon engaging diseased cells in the treatment of ovarian cancer. There are various advantages of using K562 cells throughout this process. First, Food and Drug Administration approves the reinfusion of K562 cells into patients’ bodies. Second, K562 cells are more affordable than T lymphocytes, and finally, these cells can be easily manipulated with any desired genetic material and can keep the expression of engineered genes stable. However, they do not express a chemokine receptor, a type of cytokine controlling the traffic of the immune cells to a desired site of the body. Therefore, these cells must be manipulated with chemokine receptors to enable them to migrate directly towards the tumor microenvironment to prevent harm to the healthy parts of the body. For the manipulation of all cells used in this study, lentiviruses were produced to transduce them. Nanoluc luciferase reporter was used as an effector protein to evaluate whether K562 cells can synthesize these enzymes in situ upon interacting with diseased cells. K562 cells lack necessary molecules that would drive them to form an immunological synapse to produce engineered proteins. As a result, they were not able to produce the Nanoluc enzyme. On the other hand, this study shows that the chemokine system presents an excellent potential for immunotherapies, and it may help prevent damage to healthy tissue.

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