Date of Award
Master of Science (MS)
Kamaljit Kaur, PhD.
Sun Yang, B.S. Pharmacy, Ph.D.
Aftab Ahmed, Ph.D.
Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years as a result of this concerted drug development effort; however, this rapid development of treatment technologies come with new severe adverse effects, as well as increased opportunity for toxicity and drug resistance. It is not uncommon for a treatment to switch before originally projected due to lack of patient therapeutic response to a typical cytotoxic drug. One novel method to avoid this effect is use of a peptide delivery system, essentially increasing its targeted delivery. In this thesis, a ligand, dubbed KK-11b (sequence: CVPWxEPAYQrFL), synthetically made to form a cell-specific, noncytotoxic 13-mer peptide residue, is conjugated to a linker, sulfo-SMCC, and chemotherapeutic drug doxorubicin. Together, these form a new family of targeted drug therapies: peptide-drug conjugates (PDCs). The development and characterization are discussed, its stability analyzed, and, finally, preliminary in vitro melanoma cell studies were conducted. Overall, KK-11b stability was constant, remaining present in serum-free cell media, water, and preliminary in vitro A375 melanoma cell studies. More analysis will be conducted to test the cytotoxicity of KK-11 conjugate in alternate types of melanoma cells, as well as in the presence of human serum, before ultimately progressing to in vivo murine studies if results remain promising.
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Dill, C. L. The Development of a Cancer-Targeting Peptide-Drug Conjugate for the Treatment of Melanoma. [master’s thesis]. Irvine, CA: Chapman University. https://doi.org/10.36837/chapman.000201
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