Date of Graduation

5-2013

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor

Zaharoff, David A.

Reader

Wochok, Jeffrey C.

Second Reader

Hestekin, Christa N.

Abstract

Cancer immunotherapy has emerged as a leading front in cancer treatment. In contrast to other treatment methods such as radiation and surgery, immunotherapy trains the patient's body to recognize and eliminate tumors, thus preventing reoccurrence of secondary tumors. IL-12 has been shown to display a potent anti-tumor immune response in mice; however, when clinical trials were conducted, it was shown to be toxic and in some cases fatal when administered systemically.1,2 Because of this, local delivery of IL-12 is under investigation. Our lab has shown that when paired with the polymer chitosan, local, intratumoral (i.t.) injections of IL-12 are retained in the tumor microenvironment and can lead to the elimination of tumors and generate tumor specific immune cells while reducing toxicity.3,4 In the present study, these previous findings are expanded upon and the potential for the coformulation of chitosan and IL-12 (chitosan/IL-12) to control metastasis is evaluated in a highly metastatic mammary adenocarcinoma model, 4T1. Mice treated with chitosan/IL-12 neoadjuvant to primary tumor resection showed increased survival rate when compared to mice treated with IL-12 alone. Mice treated with chitosan/IL-12 were then shown to contain fewer lung metastases. Moreover, a clinically relevant means of confirming immunity via delayed type hypersensitivity (DTH) response was observed in cured mice. Toxicology analysis also indicated that intratumoral chitosan/IL-12 induced minimal toxicity. This study demonstrated that neoadjuvant chitosan/IL-12 prior to tumor resection is safe and can generate an anti-tumor response that offers protection from metastatic disease.

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