{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:46:00Z","timestamp":1753868760152,"version":"3.41.2"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":333,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008018","name":"Victorian Cancer Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows <jats:italic>in vitro<\/jats:italic> synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa\u2010restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM <jats:italic>via<\/jats:italic> multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation <jats:italic>in vitro<\/jats:italic>. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low\u2010dose DEX in kappa\u2010restricted relapsed\/refractory MM <jats:italic>ex vivo<\/jats:italic> and assessed association of those changes with patient outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort (<jats:italic>n<\/jats:italic>\u2009=\u200940) of patients with kappa\u2010restricted relapsed\/refractory MM, treated with KM, LEN and low\u2010dose DEX, was analysed using a mass cytometry panel that allowed identification of immune cell subsets. Clustering analyses were used to determine significant changes in immune cell populations at time periods after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found changes in five DC and 17 T\u2010cell populations throughout treatment. We showed an increase in activated conventional DC populations, a decrease in immature\/precursor DC populations, a decrease in activated CD4 T cells and an increase in effector\u2010memory CD4 T cells and effector CD8 T cells, indicating an activated immune response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data characterise the effects of LEN, DEX, and KM treatment on non\u2010target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms <jats:italic>via<\/jats:italic> immune cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1478","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T15:25:13Z","timestamp":1701357913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in immune cell populations following KappaMab, lenalidomide and low\u2010dose dexamethasone treatment in multiple myeloma"],"prefix":"10.1002","volume":"12","author":[{"given":"Samuel E","family":"Norton","sequence":"first","affiliation":[{"name":"Nanix Limited  Dunedin New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Khong","sequence":"additional","affiliation":[{"name":"Myeloma Research Group, Australian Centre for Blood Diseases Alfred Hospital\u2010Monash University  Melbourne VIC 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