{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:06:24Z","timestamp":1784739984363,"version":"3.55.0"},"reference-count":30,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,7,30]]},"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Despite significant progress in the development of T cell-engaging therapies for various B-cell malignancies, a high medical need remains for the refractory disease setting, often characterized by suboptimal target levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To address this issue, we have developed a 65-kDa multispecific antibody construct, CLN-978, with affinities tuned to optimize the killing of low-CD19 expressing tumor cells. CLN-978 bound to CD19 on B cells with picomolar affinity, and to CD3\u03b5 on T cells with nanomolar affinity. A serum albumin binding domain was incorporated to extend serum half-life. In this setting, we biophysically characterize and report the activities of CLN-978 in cell co-culture assays, multiple mouse models and non-human primates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Human T cells redirected by CLN-978 could eliminate target cells expressing less than 300 copies of CD19 on their surface. The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978. In primates, we observed a long serum half-life, deep and sustained depletion of normal B cells, and remarkable tolerability, in particular, reduced cytokine release when CLN-978 was administered subcutaneously.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CLN-978 warrants further exploration. An ongoing clinical phase 1 trial is investigating safety, pharmacokinetics, pharmacodynamics, and the initial therapeutic potential of subcutaneously administered CLN-978 in patients with non-Hodgkin\u2019s lymphoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2023-007398","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T13:20:38Z","timestamp":1692192038000},"page":"e007398","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["CLN-978, a novel half-life extended CD19\/CD3\/HSA-specific T cell-engaging antibody construct with potent activity against B-cell malignancies with low CD19 expression"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8057-664X","authenticated-orcid":false,"given":"Kristan","family":"Meetze","sequence":"first","affiliation":[{"name":"Cullinan Oncology Inc, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-6750","authenticated-orcid":false,"given":"Naveen K","family":"Mehta","sequence":"additional","affiliation":[{"name":"Cullinan Oncology Inc, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochong","family":"Li","sequence":"additional","affiliation":[{"name":"Cullinan Oncology Inc, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M","family":"Findlay","sequence":"additional","affiliation":[{"name":"Antibody Analytics, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B","family":"London","sequence":"additional","affiliation":[{"name":"Antibody Analytics, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agapitos","family":"Patakas","sequence":"additional","affiliation":[{"name":"Antibody Analytics, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S","family":"Michaelson","sequence":"additional","affiliation":[{"name":"Cullinan Oncology Inc, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick A","family":"Baeuerle","sequence":"additional","affiliation":[{"name":"Cullinan Oncology Inc, Cambridge, Massachusetts, USA"},{"name":"Institute of Immunology, Ludwig-Maximilians-Universitat Munchen, Planegg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"2025100302340500000_11.8.e007398.1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1609783"},{"key":"2025100302340500000_11.8.e007398.2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s11864-021-00925-1","article-title":"Bispecific antibodies for non-Hodgkin lymphoma treatment","volume":"23","author":"Bock","year":"2022","journal-title":"Curr Treat Options Oncol"},{"key":"2025100302340500000_11.8.e007398.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1586"},{"key":"2025100302340500000_11.8.e007398.4","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1182\/bloodadvances.2020002393","article-title":"Teclistamab is an active T cell\u2013redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma","volume":"4","author":"Pillarisetti","year":"2020","journal-title":"Blood Adv"},{"key":"2025100302340500000_11.8.e007398.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142859"},{"key":"2025100302340500000_11.8.e007398.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.02.013"},{"key":"2025100302340500000_11.8.e007398.7","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3109\/10428194.2016.1161185","article-title":"Blinatumomab: a CD19\/CD3 bispecific T cell engager (bite) with unique anti-tumor efficacy","volume":"57","author":"Goebeler","year":"2016","journal-title":"Leuk Lymphoma"},{"key":"2025100302340500000_11.8.e007398.8","doi-asserted-by":"crossref","DOI":"10.1038\/bcj.2016.84","article-title":"Blinatumomab vs historical standard therapy of adult relapsed\/refractory acute lymphoblastic leukemia","volume":"6","author":"G\u00f6kbuget","year":"2016","journal-title":"Blood Cancer J"},{"key":"2025100302340500000_11.8.e007398.9","doi-asserted-by":"crossref","unstructured":"Topp MS , G\u00f6ckbuget N , Stein AS . 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