<i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy
The therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8<sup>+</sup> T cell-mediated antican...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/11/2/471 |
| _version_ | 1797396745753198592 |
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| author | Jihoon Kim David M. Francis Susan N. Thomas |
| author_facet | Jihoon Kim David M. Francis Susan N. Thomas |
| author_sort | Jihoon Kim |
| collection | DOAJ |
| description | The therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8<sup>+</sup> T cell-mediated anticancer immunity. However, low rates of patient responses and the high rate of immune-related adverse events remain significant challenges to broadening the benefit of this therapeutic class, termed immune checkpoint blockade (ICB). To overcome these significant limitations, controlled delivery and release strategies offer unique advantages relevant to this therapeutic class, which is typically administered systemically (e.g., intravenously), but more recently, has been shown to be highly efficacious using locoregional routes of administration. As such, in this paper, we describe an <i>in situ</i> crosslinked hydrogel for the sustained release of antibodies blocking CTLA-4 and PD-1 signaling from a locoregional injection proximal to the tumor site. This formulation results in efficient and durable anticancer effects with a reduced systemic toxicity compared to the bolus delivery of free antibody using an equivalent injection route. This formulation and strategy thus represent an approach for achieving the efficient and safe delivery of antibodies for ICB cancer immunotherapy. |
| first_indexed | 2024-03-09T00:56:04Z |
| format | Article |
| id | doaj.art-d8097ab214e2479296e9b9c49c31c657 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-09T00:56:04Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-d8097ab214e2479296e9b9c49c31c6572023-12-11T16:54:37ZengMDPI AGNanomaterials2079-49912021-02-0111247110.3390/nano11020471<i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer ImmunotherapyJihoon Kim0David M. Francis1Susan N. Thomas2Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USAParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USAParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USAThe therapeutic inhibition of immune checkpoints, including cytotoxic T lymphocyte-associated protein (CTLA)-4 and programmed cell death 1 (PD-1), through the use of function blocking antibodies can confer improved clinical outcomes by invigorating CD8<sup>+</sup> T cell-mediated anticancer immunity. However, low rates of patient responses and the high rate of immune-related adverse events remain significant challenges to broadening the benefit of this therapeutic class, termed immune checkpoint blockade (ICB). To overcome these significant limitations, controlled delivery and release strategies offer unique advantages relevant to this therapeutic class, which is typically administered systemically (e.g., intravenously), but more recently, has been shown to be highly efficacious using locoregional routes of administration. As such, in this paper, we describe an <i>in situ</i> crosslinked hydrogel for the sustained release of antibodies blocking CTLA-4 and PD-1 signaling from a locoregional injection proximal to the tumor site. This formulation results in efficient and durable anticancer effects with a reduced systemic toxicity compared to the bolus delivery of free antibody using an equivalent injection route. This formulation and strategy thus represent an approach for achieving the efficient and safe delivery of antibodies for ICB cancer immunotherapy.https://www.mdpi.com/2079-4991/11/2/471intradermal immunotherapyimmune checkpoint blockadessustained release<i>in situ</i> crosslinked hydrogel |
| spellingShingle | Jihoon Kim David M. Francis Susan N. Thomas <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy Nanomaterials intradermal immunotherapy immune checkpoint blockades sustained release <i>in situ</i> crosslinked hydrogel |
| title | <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy |
| title_full | <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy |
| title_fullStr | <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy |
| title_full_unstemmed | <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy |
| title_short | <i>In Situ</i> Crosslinked Hydrogel Depot for Sustained Antibody Release Improves Immune Checkpoint Blockade Cancer Immunotherapy |
| title_sort | i in situ i crosslinked hydrogel depot for sustained antibody release improves immune checkpoint blockade cancer immunotherapy |
| topic | intradermal immunotherapy immune checkpoint blockades sustained release <i>in situ</i> crosslinked hydrogel |
| url | https://www.mdpi.com/2079-4991/11/2/471 |
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