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Title: ?Melanoma Targeted Radio- and Non-small Cell Lung Cancer Targeted Immunopharmaceuticals?

Abstract: Aberrant growth signaling and tumor mediated immunosuppression are two of the ten hallmarks of cancer(1). A result of aberrant growth signaling is higher expression of receptors on tumor cells relative to normal cells; this phenomenon is the basis for well established examples of in vivo imaging using PET, SPECT, or fluorescently labeled agents or cytotoxic payload delivery to targeted tumors using peptide targeting ligands or antibodies as affinity reagents, e.g. antibody-drug conjugates(2). This seminar will report our latest efforts to concentrate highly lethal alpha particle emitters or potent immunotherapy agents at targeted tumors.  Although these two approaches to cancer treatment are not usually considered together, it is our goal to do so.  Both highly lethal alpha emitters and immunotherapy can be administered as systemic doses that can be molecularly targeted to concentrate at the tumor microenvironment and these targeted agents should reduce systemic exposure relative to untargeted agents and provide a greater therapeutic index. Specifically, we will present our results using the melanocortin 1 receptor ligand conjugated to DOTA-Ac-225 as a high affinity, high specificity melanoma cell binder, and its safe and effective activity against cutaneous and uveal melanomas in vivo.  We will also present our work on the use of the delta opioid receptor (DOR) ligand conjugated with anti-PD1, its high affinity, high specificity lung cancer cell binding, and in vivo imaging showing its greater accumulation at DOR positive relative to DOR negative non-small cell lung tumors in vivo.

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[[lrashburne]]

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