Lymphatic immunomodulation using engineered drug delivery systems for cancer immunotherapy

• Type of Material: Article
• Authors: Margaret P Manspeaker, Georgia Institute of Technology; Susan N Thomas, Emory University
• Language: English
• Date: 2020-10-12
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Elsevier B.V. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.addr.2020.10.004
• Title of Journal or Parent Work: ADVANCED DRUG DELIVERY REVIEWS
• Volume: 160
• Start Page: 19
• End Page: 35
• Grant/Funding Information: This work was supported by National Institutes of Health (NIH) Grants R01CA207619 and R01CA247484, Department of Defense Grant CA150523, and the Curci Foundation. M.P.M. was supported by a National Science Foundation Graduate Research Fellowship.
• Keywords: tumor immunotherapy; drug delivery system; immunoengineering; lymph node; controlled release; lymphatics

Abstract

Though immunotherapy has revolutionized the treatment of cancer to improve disease outcomes, an array of challenges remain that limit wider clinical success, including low rate of response and immune-related adverse events. Targeting immunomodulatory drugs to therapeutically relevant tissues offers a way to overcome these challenges by potentially enabling enhanced therapeutic efficacy and decreased incidence of side effects. Research highlighting the importance of lymphatic tissues in the response to immunotherapy has increased interest in the application of engineered drug delivery systems (DDSs) to enable specific targeting of immunomodulators to lymphatic tissues and cells that they house. To this end, a variety of DDS platforms have been developed that enable more efficient uptake into lymphatic vessels and lymph nodes to provide targeted modulation of the immune response to cancer. This can occur either by delivery of immunotherapeutics to lymphatics tissues or by direct modulation of the lymphatic vasculature itself due to their direct involvement in tumor immune processes. This review will highlight DDS platforms that, by enabling the activities of cancer vaccines, chemotherapeutics, immune checkpoint blockade (ICB) antibodies, and anti- or pro-lymphangiogenic factors to lymphatic tissues through directed delivery and controlled release, augment cancer immunotherapy.