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.
","abstract_html":"<p>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 <em>in vitro</em> melanoma cell studies were conducted. Overall, KK-11b stability was constant, remaining present in serum-free cell media, water, and preliminary <em>in vitro</em> 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 <em>in vivo</em> murine studies if results remain promising.</p>","abstract_has_math":false,"creators":["Dill, Cassandra"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Pharmaceutical Sciences","degree_department":null,"school":null,"contributors":["Kamaljit Kaur, PhD.","Sun Yang, B.S. Pharmacy, Ph.D.","Aftab Ahmed, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-01-01T08:00:00Z","date_published":"2021-01-01T08:00:00Z","updated_at":"2026-07-24T01:38:09Z","subjects":["peptide-drug conjugate","melanoma","Medicinal and Pharmaceutical Chemistry","Other Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.chapman.edu/pharmaceutical_sciences_theses/14","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kamaljit Kaur, PhD.","Sun Yang, B.S. 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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.
"]},{"key":"dc:source","label":"Dc Source","values":["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"]},{"key":"dc:title","label":"Title","values":["The Development of a Cancer-Targeting Peptide-Drug Conjugate for the Treatment of Melanoma"]}]}],"canonical_facts":{"dc:contributor":["Kamaljit Kaur, PhD.","Sun Yang, B.S. Pharmacy, Ph.D.","Aftab Ahmed, Ph.D."],"dc:creator":["Dill, Cassandra"],"dc:date.available":["2021-08-31T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.chapman.edu/pharmaceutical_sciences_theses/14"],"dc:source":["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"],"dc:subject":["peptide-drug conjugate","melanoma","Medicinal and Pharmaceutical Chemistry","Other Pharmacy and Pharmaceutical Sciences"],"dc:title":["The Development of a Cancer-Targeting Peptide-Drug Conjugate for the Treatment of Melanoma"],"thesis:degree_discipline":["Pharmaceutical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T01:38:09Z"}