Professor of Biological Engineering and Materials Science & Engineering
Associate Director, Koch Institute for Integrative Cancer Research
Member, Marble Center for Cancer Nanomedicine
Investigator, Howard Hughes Medical Institute
KI Research Areas of Focus:
Nano-based Drugs, Cancer Immunology
"Our laboratory works at the interface of materials science and immunology. We use synthetic model systems to study immune cell biology and synthesize new materials for vaccines and immunotherapy. Building on our work on the mechanisms of T and B cell migration, we have developed chemokine-releasing microparticles that are informing our research and may represent a new tool for immunotherapy. We are also studying nanoparticles to overcome some of the key challenges in immunotherapy."
Learn more about the work going on in the Irvine lab, which focuses on development of drug delivery tools and new methods for analyzing cellular immune responses, by watching this video: "Inside the Lab: Darrell J. Irvine, Ph.D."
The Irvine lab's work is profiled as part of the current interactive exhibits in the Koch Institute Public Galleries. Watch a web version of the story here.
Darrell Irvine is a Professor at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. He also serves on the steering committee of the Ragon Institute of MGH, MIT, and Harvard. His research is focused on the application of engineering tools to problems in cellular immunology and the development of new materials for vaccine and drug delivery. Current efforts are focused on problems related to vaccine development for HIV and immunotherapy of cancer. This interdisciplinary work has been recognized in numerous awards, including a Beckman Young Investigator award, an NSF CAREER award, selection for Technology Review’s ‘TR35’, election as a Fellow of the Biomedical Engineering Society, and appointment as an investigator of the Howard Hughes Medical Institute. He is the author of over 70 publications, reviews, and book chapters and an inventor on numerous patents.
The Irvine laboratory works at the interface of materials science and immunology. They use synthetic model systems to study immune cell biology and synthesize new materials for vaccines/immunotherapy, using a mechanistic understanding of the immune system to guide the design of these materials. They have pioneered the use of patterned surfaces as tools to dissect T-cell activation, using the ability to control the density, placement, and mobility of T-cell ligands, supported membranes, or entire cells on surfaces to dissect the functions of the immunological synapse in T-cell triggering. In a second focus, they study leukocyte chemotaxis/chemokinesis; they have discovered novel mechanisms for chemokine-mediated control of naïve lymphocyte migration, and shown that both T-cell and B cell migration in secondary lymphoid organs may be regulated by a complex interplay of chemokinesis and chemotaxis. Building on these fundamental findings, they have developed chemokine-releasing microparticles and hydrogels as tools to study immune cell migration and adjuvants to modulate cell migration in vaccines and immunotherapy. Finally, they have developed nanoparticles that can address key challenges in immunotherapy: (i) vaccine particles that co-deliver high doses of antigen in concert with immunostimulatory ligands, (ii) nanoparticles that deliver proteins or oligonucleotides to the cytosol of dendritic cells without cytotoxicity, and (iii) synthetic particles with surfaces structurally mimicking the envelope of pathogens.
Mandal A, Boopathy AV, Lam LKW, Moynihan KD, Welch ME, Bennett NR, Turvey ME, Thai N, Van JH, Love JC, Hammond PT, and Irvine DJ, “Cell- and Fluid-Sampling Microneedle Patches for Monitoring Tissue- Resident Immunity,” Science Translational Medicine. 2018. 10(467) eaar2227 1-14. doi:10.1126/scitranslmed.aar2227
Moynihan KD, Holden RL, Mehta NK, Wang C, Karver MR, Dinter J, Liang S, Abraham W, Melo MB, Zhang AQ, Li N, Le Gall S, Pentelute BL, and Irvine DJ, “Enhancement of Peptide Vaccine Immunogenicity by Increasing Lymphatic Drainage and Boosting Serum Stability,” Cancer Immunology Research. 2018. 6(9):1025-1038. PMCID: PMC6247902. doi:10.1158/2326-6066.CIR-17-0607
Tang L, Zheng Y, Melo M, Mabardi L, Castaño AP, Xie Y-Q, Li N, Kudchodkar SB, Wong HC, Jeng EK, Maus MV, and Irvine DJ, “Enhancing T-cell therapy through TCR signaling-responsive nanoparticle drug delivery,” Nature Biotechnology. 2018. 36(8):707-716. PMCID: PMC6078803. doi:10.1038/nbt.4181
Zhang Y, Li N, Suh H, and Irvine DJ. Nanoparticle anchoring targets immune agonists to tumors enabling anti-cancer immunity without systemic toxicity. Nature Communications 2018. 9(1):6. PMCID: PMC5750237. doi:10.1038/s41467-017-02251-3
Daniela Schmid, Chun Gwon Park, Christina A. Hartl, Nikita Subedi, Adam N. Cartwright, Regina Bou Puerto, Yiran Zheng, James Maiarana, Gordon J. Freeman, Kai W. Wucherpfennig, Darrell J. Irvine, Michael S. Goldberg. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nat. Commun. 2017. 8(1): 1–11. PMCID: PMC5700944. doi:10.1038/s41467-017-01830-8
Alice Tzeng, Monique J. Kauke, Eric F. Zhu, Kelly D. Moynihan, Cary F. Opel, Nicole J. Yang, Naveen Mehta, Ryan L. Kelly, Gregory L. Szeto, Willem W. Overwijk, Darrell J. Irvine, K. Dane Wittrup. Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy. Cell Reports. 2016. 17(10): 2503-2511. PMCID: PMC5204262. doi:10.1016/j.celrep.2016.11.020
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, and Darrell J Irvine. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat. Med. 2016. PMCID: PMC5209798. doi:10.1038/nm.4200
B. Huang, W. D. Abraham, Y. Zheng, S. C. Bustamante López, S. S. Luo, D. J. Irvine. Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells. Sci. Transl. Med. 2015. 7, 291ra94. PMCID: PMC4687972. doi:10.1126/scitranslmed.aaa5447
Hanson MC, Crespo MP, Abraham W, Moynihan KD, Szeto GL, Chen SH, Melo MB, Mueller S, and Irvine DJ. Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants. Journal of Clinical Investigation. 2015. 125(6):2532-46. PMCID: PMC4497758. doi:10.1172/JCI79915
Liu H, Moynihan K, Zheng Y, Szeto G, Li A, Huang B, Egeren D, Park C, Irvine D. Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 2014. 507(7493): 519–522. PMCID: PMC4069155. doi:10.1038/nature12978
