@article{4918a6c6f55a40fd85376bb94143302a,
title = "Targeted phage display-based pulmonary vaccination in mice and non-human primates",
abstract = "Background: The extensive alveolar capillary network of the lungs is an attractive route for the administration of several agents. One key functional attribute is the rapid onset of systemic action due to the absence of first-pass metabolism. Methods: Here, we applied a combinatorial approach for ligand-directed pulmonary delivery as a unique route for systemic targeting in vaccination. Findings: We screened a phage display random peptide library in vivo to select, identify, and validate a ligand (CAKSMGDIVC) that specifically targets and is internalized through its receptor, α3β1 integrin, on the surface of cells lining the lung airways and alveoli and mediates CAKSMGDIVC-displaying phage binding and systemic delivery without compromising lung homeostasis. As a proof-of-concept, we show that the pulmonary delivery of targeted CAKSMGDIVC-displaying phage particles in mice and non-human primates elicits a systemic and specific humoral response. Conclusions: This broad methodology blueprint represents a robust and versatile platform tool enabling new ligand-receptor discovery with many potential translational applications. Funding: Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center ( CA016672), University of New Mexico Comprehensive Cancer Center ( CA118100), Rutgers Cancer Institute of New Jersey ( CA072720), research awards from the Gillson-Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.",
keywords = "delivery, Foundational Research, inhalation, lung, non-human primate, phage display, vaccination",
author = "Staquicini, {Daniela I.} and Barbu, {E. Magda} and Zemans, {Rachel L.} and Dray, {Beth K.} and Staquicini, {Fernanda I.} and Prashant Dogra and Marina Card{\'o}-Vila and Miranti, {Cindy K.} and Baze, {Wallace B.} and Villa, {Luisa L.} and Jorge Kalil and Geetanjali Sharma and Prossnitz, {Eric R.} and Zhihui Wang and Vittorio Cristini and Sidman, {Richard L.} and Berman, {Andrew R.} and Panettieri, {Reynold A.} and Tuder, {Rubin M.} and Renata Pasqualini and Wadih Arap",
note = "Funding Information: The authors wish to thank Mr. Daniel F. Cimino, Dr. Sara D{\textquoteright}Angelo, Dr. Andrey S. Dobroff, Dr. Fortunato Ferrara, Ms. Nicole Jansen, Dr. Serena Marchi{\`o}, Dr. Pavan Muttil, Ms. Huynh Nguyen, Mr. Paul O{\textquoteright}Brien, Dr. Tracey L. Smith, Ms. Christy A. Tarleton, Ms. Mayra V. Tuiche, and Dr. Virginia J. Yao for technical assistance and helpful insights. We also thank Dr. Helen Pickersgill (Life Science Editors) for professional editorial services and Dr. Pravin B. Sehgal for critical reading of the manuscript. This work was supported in part by core services from Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center ( CA016672 ), University of New Mexico Comprehensive Cancer Center ( CA118100 ), Rutgers Cancer Institute of New Jersey ( CA072720 ), and by research awards from the Gillson-Longenbaugh Foundation (to R.P. and W.A.). This work has also been supported in part by the National Institutes of Health (NIH) Grant 1R01CA226537 (Z.W., V.C., R.P., W.A.). Funding Information: Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), research awards from the Gillson-Longenbaugh Foundation, and National Institutes of Health (NIH) grant no. 1R01CA226537.The authors wish to thank Mr. Daniel F. Cimino, Dr. Sara D'Angelo, Dr. Andrey S. Dobroff, Dr. Fortunato Ferrara, Ms. Nicole Jansen, Dr. Serena Marchi?, Dr. Pavan Muttil, Ms. Huynh Nguyen, Mr. Paul O'Brien, Dr. Tracey L. Smith, Ms. Christy A. Tarleton, Ms. Mayra V. Tuiche, and Dr. Virginia J. Yao for technical assistance and helpful insights. We also thank Dr. Helen Pickersgill (Life Science Editors) for professional editorial services and Dr. Pravin B. Sehgal for critical reading of the manuscript. This work was supported in part by core services from Cancer Center Support Grants to the University of Texas M.D. Anderson Cancer Center (CA016672), University of New Mexico Comprehensive Cancer Center (CA118100), Rutgers Cancer Institute of New Jersey (CA072720), and by research awards from the Gillson-Longenbaugh Foundation (to R.P. and W.A.). This work has also been supported in part by the National Institutes of Health (NIH) Grant 1R01CA226537 (Z.W. V.C. R.P. W.A.). D.I.S. E.M.B. R.L.Z. B.K.D. F.I.S. P.D. Z.W. V.C. R.A.P. Jr. R.M.T. R.P. and W.A. designed the research; D.I.S. E.M.B. R.L.Z. B.K.D. F.I.S. P.D. M.C.-V. W.B.B. G.S. Z.W. and V.C. performed the research; C.K.M. L.L.V. J.K. E.R.P. Z.W. V.C. R.L.S. A.R.B. and R.A.P. Jr. contributed concepts, reagents, or analytical tools; D.I.S. E.M.B. R.L.Z. B.K.D. F.I.S. P.D. M.C.-V. C.K.M. W.B.B. L.L.V. J.K. G.S. E.R.P. Z.W. V.C. R.L.S. A.R.B. R.A.P. Jr. R.M.T. R.P. and W.A. analyzed the data; D.I.S. E.M.B. R.L.Z. P.D. Z.W. V.C. R.L.S. R.M.T. R.P. and W.A. wrote the initial draft of the manuscript, to which all of the authors contributed edits. R.P. and W.A. supervised the overall project. D.I.S. E.M.B. R.P. and W.A. are listed as inventors on a patent application related to this technology (International Patent Application no. PCT/US2020/053758, entitled ?Targeted Pulmonary Delivery Compositions and Methods Using Same?). R.P. and W.A. are founders and equity stockholders of PhageNova Bio, which has licensed this intellectual property, and the inventors are entitled to standard royalties if commercialization occurs. R.P. is Chief Scientific Officer and a paid consultant of PhageNova Bio. R.P. and W.A. are founders and shareholders of MBrace Therapeutics. R.P. serves as Chief Scientific Officer and a board member and W.A. is head of the Scientific Advisory Board. These arrangements are managed in accordance with the established institutional conflict of interest policies of Rutgers, The State University of New Jersey. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc. Copyright: Copyright 2022 Elsevier B.V., All rights reserved.",
year = "2021",
month = mar,
day = "12",
doi = "10.1016/j.medj.2020.10.005",
language = "English (US)",
volume = "2",
pages = "321--342.e8",
journal = "Med",
issn = "2666-6359",
publisher = "Cell Press",
number = "3",
}