{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:16:57Z","timestamp":1787314617269,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute of the National Institutes of Health","doi-asserted-by":"publisher","award":["5R37CA239150"],"award-info":[{"award-number":["5R37CA239150"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Focused Ultrasound Foundation, PETCO, and the Kerr (Ranjan) Endowed Chair at Oklahoma State University","award":["5R37CA239150"],"award-info":[{"award-number":["5R37CA239150"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated \u2018hot\u2019 targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (&gt;70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model.<\/jats:p>","DOI":"10.3390\/pharmaceutics15061693","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"1693","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Overcoming Resistance to Immune Checkpoint Inhibitor Therapy Using Calreticulin-Inducing Nanoparticle"],"prefix":"10.3390","volume":"15","author":[{"given":"Sri Vidhya","family":"Chandrasekar","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-4157","authenticated-orcid":false,"given":"Akansha","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8851-496X","authenticated-orcid":false,"given":"Ashish","family":"Ranjan","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, College of Veterinary, Oklahoma State University, Stillwater, OK 74078, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sato, Y., Fu, Y., Liu, H., Lee, M.Y., and Shaw, M.H. 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