89Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding

Emilie M.J. van Brummelen, Marc C. Huisman, Linda J. de Wit-van der Veen, Tapan K. Nayak, Marcel P.M. Stokkel, Emma R. Mulder, Otto S. Hoekstra, Danielle J. Vugts, Guus A.M.S. Van Dongen, Henk M. Verheul, Stefan Evers, Jean J.L. Tessier, Jose Saro, Jan H.M. Schellens, C. Willemien Menke-van der Houven van Oordt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) a binding. We describe the biodistribution and tumor accumulation of 89Zr-labeled CEA-IL2v. Twenty-four patients with advanced solid CEA positive (CEA+) or negative (CEA-) tumors received CEA-IL2v 6 mg (4 CEA+; 3 CEA-), 20 mg (9 CEA+), or 30 mg (4 CEA+; 4 CEA-) biweekly. In cycle 1, 2 mg of the total dose comprised 89Zr-CEA-IL2v (50 MBq) and serial 89Zr-PET imaging was conducted. Four CEA+ patients with visually confirmed 89Zr-CEA-IL2v tumor accumulation at 20 mg had repeated 89Zr-PET imaging during cycle 4. 89Zr-CEA-IL2v immuno-PET demonstrated preferential drug accumulation in CEA+ tumors (%ID/mLpeak CEA- 3.6 × 10-3 vs. CEA+ 6.7 ×·10-3). There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses ≥20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding. Reduced exposure and reduced tumor accumulation (%ID/mLpeak 57% lower) on cycle 4 vs. cycle 1 was consistent with peripheral expansion of immune cells. The findings of this immune PET imaging study with 89Zr-CEA-IL2v support the therapeutic concept of CEA-IL2v, confirming selective and targeted tumor accumulation with this novel immunocytokine.

Original languageEnglish
Pages (from-to)24737-24749
Number of pages13
JournalOncotarget
Volume9
Issue number37
DOIs
Publication statusPublished - 15 May 2018

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