A nano-enhanced vaccine for metastatic melanoma immunotherapy  

作　　者：Katelyn E.Salotto Walter C.Olson Jr Karlyn E.Pollack Anuradha Illendula Elishama Michel Sydney Henriques Todd Fox Susan Walker Marya Dunlap-Brown Craig L.Slingluff Jr Mark Kester Helena W.Snyde 

机构地区：[1]School of Engineering and Applied Sciences,University of Virginia,Virginia,VA 22904,USA [2]Department of Surgery,School of Medicine,University of Virginia,Virginia,VA 22903,USA [3]Department of Dermatology,School of Medicine,University of Virginia,Virginia,VA 22903,USA [4]Department of Pharmacology,School of Medicine,University of Virginia,Virginia,VA 22903,USA [5]University of Virginia nanoSTAR Institute,Virginia,VA 22903,USA [6]Molecular Immunologic&Translational Sciences(MITS)Core,School of Medicine,University of Virginia,Virginia,VA 22903,USA [7]Department of Materials Science,School of Engineering and Applied Sciences,University of Virginia,Virginia,VA 22903,USA

出　　处：《Cancer Drug Resistance》2022年第3期829-845,共17页癌症耐药（英文）

摘　　要：Aim:Despite the huge advancements in cancer therapies and treatments over the past decade,most patients with metastasized melanoma still die from the disease.This poor prognosis largely results from resistance to conventional chemotherapies and other cytotoxic drugs.We have previously identified 6 antigenic peptides derived from melanomas that have proven efficacious for activating CD4+T cells in clinical trials for melanoma.Our aim was to improve pharmacodynamics,pharmacokinetic and toxicological parameters by individually encapsulating each of the 6 melanoma helper peptides within their own immunogenic nanoliposomes.Methods:We modified these liposomes as necessary to account for differences in the peptides’chemical properties,resulting in 3 distinct formulations.To further enhance immunogenicity,we also incorporated KDO2,a TLR4 agonist,into the lipid bilayer of all nanoliposome formulations.We then conducted in vivo imaging studies in mice and ex vivo cell studies from 2 patient samples who both strongly expressed one of the identified peptides.Results:We demonstrate that these liposomes,loaded with the different melanoma helper peptides,can be readily mixed together and simultaneously delivered without toxicity in vivo.These liposomes are capable of being diffused to the secondary lymphoid organs very quickly and for at least 6 days.In addition,we show that these immunogenic liposomes enhance immune responses to specific peptides ex vivo.Conclusion:Lipid-based delivery systems,including nanoliposomes and lipid nanoparticles,have now been validated for pharmacological(small molecules,bioactive lipids)and molecular(mRNA,siRNA)therapeutic approaches.However,the utility of these formulations as cancer vaccines,delivering antigenic peptides,has not yet achieved the same degree of commercial success.Here,we describe the novel and successful development of a nanoliposome-based cancer vaccine for melanoma.These vaccines help to circumvent drug resistance by increasing a patient’s T cell response,making them more s

关 键 词：NANOLIPOSOMES nanoscale drug delivery cancer vaccines metastasized melanoma PEPTIDES melanoma drug resistance 

分 类 号：R73[医药卫生—肿瘤]