{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T13:29:06Z","timestamp":1787232546761,"version":"build-2736575974"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":69,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS","award":["U01FD005938"],"award-info":[{"award-number":["U01FD005938"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Copanlisib is a pan-phosphoinositide-3-kinase-inhibitor originally indicated for adult patients with relapsed follicular lymphoma who had received at least two prior systemic therapies. At the time this study was conducted, it was approved for use by the FDA and was being evaluated in clinical trials in combination therapy with checkpoint inhibitors for a range of cancers.<\/jats:p>\n                  <jats:p>Prior to conducting studies with the combination of copanlisib and checkpoint inhibitors, we conducted a pilot study to determine route of administration, identify an appropriate dose, and assess the effects of copanlisib in bone marrow-liver-thymus (BLT) immune-humanized mice. We tested three doses of copanlisib via two routes of administration in humanized mice produced from three unique donors and evaluated tissue-based toxicity via histopathology and immune changes with flow cytometry.<\/jats:p>\n                  <jats:p>Histopathology showed no significant correlation in pathological findings based on copanlisib dose or administration route. However, analysis of the histopathology by donor revealed clear differences, with one donor showing significant pathology, regardless of treatment dose or route, while the other two donors showed little to no adverse treatment effects. Flow cytometric analysis showed the affected donor had significantly more activated T-cells present in the bone marrow regardless of dose or route of administration.<\/jats:p>\n                  <jats:p>Although our findings represent only one of three donors used in immune-humanized mice, this study suggests that some immune modulating therapeutic toxicity could be associated with specific genetic factors from individual patients rather than being dose related.<\/jats:p>","DOI":"10.1007\/s00262-026-04398-9","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T05:56:56Z","timestamp":1781243816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Donor-specific toxicity of copanlisib identified using immune-humanized mice"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7590-9217","authenticated-orcid":false,"given":"Robyn E.","family":"Becker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-8825","authenticated-orcid":false,"given":"Jenny","family":"R\u00e9siliac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-4357","authenticated-orcid":false,"given":"Kathleen L.","family":"Gabrielson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8466-3199","authenticated-orcid":false,"given":"Zhuoming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-754X","authenticated-orcid":false,"given":"Kristina E.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"4398_CR1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.2147\/CMAR.S201024","volume":"13","author":"AF Chauhan","year":"2021","unstructured":"Chauhan AF, Cheson BD (2021) Copanlisib in the treatment of relapsed follicular lymphoma: utility and experience from the clinic. 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Human tissues were obtained through commercial sources and were exempt from Institutional Review Board approval.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was an animal experiment using mice.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was an animal experiment using mice.","order":4,"name":"Ethics","label":"Consent for publish","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"212"}}