{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:19:39Z","timestamp":1790713179282,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T00:00:00Z","timestamp":1552003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:p>Agonistic CD40 antibodies activate dendritic cells and can expand and activate tumor\u2010specific T cells. Our purpose was to assess the CD40 agonistic antibody ADC\u20101013 in the clinical setting including intratumoral administration since preclinical studies have indicated that intratumoral is better than intravenous administration. A Phase I, open label, multicenter study was conducted in patients with advanced solid tumors who had received established treatments. A modified 3\u2009+\u20093 dose\u2010escalation was applied (every other week dosing). Twenty\u2010three patients were treated with ADC\u20101013 intratumorally (dosing from 22.5 \u03bcg\/kg up to 400\u2009\u03bcg\/kg) or intravenously (dosing at 75\u2009\u03bcg\/kg). The pharmacodynamic effects observed in the patients were further verified in an hCD40tg mouse model. Adverse events were mostly Common Terminology Criteria for Adverse Events (CTCAE) Grades 1 or 2 and transient. The serum concentration ADC\u20101013 and cytokine release (MCP\u20101, TNF\u03b1 and IL\u20106) were more pronounced in patients receiving injections in deep metastases compared to patients receiving injections in superficial metastases. Treatment with ADC\u20101013 resulted in a marked decrease in B cell levels in peripheral blood after 24\u2009h while remaining B cells significantly increased their expression of the cell surface activation marker CD86. Activation of antigen\u2010presenting cells and subsequent activation of T cells were demonstrated in hCD40tg mice. Moreover, ADC\u20101013 treatment in this mouse model acted synergistically with a PD\u20101 inhibitor. The results from the first\u2010in\u2010human study of ADC\u20101013 indicate that intratumoral administration of ADC\u20101013 into superficial lesions is well tolerated at clinically relevant doses and associated with pharmacodynamic responses.<\/jats:p>","DOI":"10.1002\/ijc.32141","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T15:19:45Z","timestamp":1548083985000},"page":"1189-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["First\u2010in\u2010human study with intratumoral administration of a CD40 agonistic antibody, ADC\u20101013, in advanced solid malignancies"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2107-7512","authenticated-orcid":false,"given":"Sandra M. M.","family":"Irenaeus","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"},{"name":"Department of Oncology Uppsala University Hospital  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorte","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Oncology Herlev\u2010Gentofte Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ellmark","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Yachnin","sequence":"additional","affiliation":[{"name":"Department of Oncology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Deronic","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneli","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Norl\u00e9n","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niina","family":"Veitonm\u00e4ki","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla S.","family":"Wennersten","sequence":"additional","affiliation":[{"name":"Alligator Bioscience AB Medicon Village  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustav J.","family":"Ullenhag","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"},{"name":"Department of Oncology Uppsala University Hospital  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.uct.2007.06.001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00782.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.02.008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.80"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2012.698338"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2064"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e31829fb856"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1198443"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2012.692844"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0913"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0152"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.710328"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.008003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.3311"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1320"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2888"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn104"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-13-0067"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082107699"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13304-014-0265-0"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","unstructured":"KelleyK GelzleichterT XieD et al.Preclinical pharmacokinetics pharmacodynamics and activity of a humanized anti\u2010CD40 antibody (SGN\u201040) in rodents and non\u2010human primatesed.2006;148:1116\u201323.","DOI":"10.1038\/sj.bjp.0706828"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.32141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32141","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:20:14Z","timestamp":1694038814000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,8]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/ijc.32141"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32141","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,8]]},"assertion":[{"value":"2018-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}