{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:33:03Z","timestamp":1767339183621,"version":"build-2065373602"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>\n                    Novel compounds targeting the adaptive immune system are commonly initially investigated in healthy volunteers (HV). HV frequently lack constitutively expressed drug\u2010target engagement biomarkers, complicating the evaluation of pharmacological activity. The keyhole limpet hemocyanin (KLH) neo\u2010antigen challenge elicits a controlled immune response in HV and is a potential model for investigating compounds targeting the adaptive immune system. A randomized, double\u2010blind, placebo\u2010controlled study in HV was conducted, investigating the effects of repeated immunizations with KLH on Days 1, 15, and 29, followed by intradermal KLH administration on Day 50. Systemically, KLH\u2010specific antibodies were evaluated. Leukocytes were stimulated\n                    <jats:italic>ex vivo<\/jats:italic>\n                    to determine KLH\u2010specific responses using ELISpot. Locally, KLH skin response was evaluated 0\u201348\u2009hours post intradermal administration, using imaging, suction blister fluid analysis, and biopsy analysis. Twelve male HV aged 18\u201342\u2009years completed the study. KLH antibody levels increased incrementally. ELISpot analyses demonstrated KLH\u2010specific IFN\u2010\u03b3 and IL\u201013 responses. Intradermal KLH injection drove a peak response 24\u2009h after administration, observed as erythema and increased perfusion. Blister fluid analysis showed cell influx (T cells; B cells; monocytes; dendritic cells) at 24\u2009h, largely decreasing at 48\u2009h, as confirmed by immunofluorescent staining of skin biopsies. These findings demonstrate a T\u2010cell\u2010mediated response to intradermal KLH that is more rapid than the classical delayed\u2010type hypersensitivity response. This study highlights the importance of the timing of measurements and combining non\u2010invasive and invasive biomarkers. The KLH neo\u2010antigen challenge model presented in this study offers a framework to study the effect of novel immunomodulatory compounds on the adaptive immune system early in clinical development.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70007","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T05:38:42Z","timestamp":1753249122000},"page":"1132-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Profiling a Neo\u2010Antigen\u2010Driven Immune Response in Healthy Volunteers: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Study of the KLH Challenge Model"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-2836","authenticated-orcid":false,"given":"Micha N.","family":"Ronner","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-108X","authenticated-orcid":false,"given":"Hendrika W.","family":"Grievink","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-0037","authenticated-orcid":false,"given":"Mahdi","family":"Saghari","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Osse","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry P.P.","family":"van den Bosch","sequence":"additional","affiliation":[{"name":"Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Damman","sequence":"additional","affiliation":[{"name":"Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marieke L.","family":"de Kam","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7912-0918","authenticated-orcid":false,"given":"Jacobus","family":"Burggraaf","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"},{"name":"Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi B.","family":"Klarenbeek","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9207-1807","authenticated-orcid":false,"given":"Manon A. 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