Oncotarget

Research Papers:

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 and C. Willemien Menke-van der Houven van Oordt _

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Oncotarget. 2018; 9:24737-24749. https://doi.org/10.18632/oncotarget.25343

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Abstract

Emilie M.J. van Brummelen1,6, Marc C. Huisman2, Linda J. de Wit-van der Veen1, Tapan K. Nayak3, Marcel P.M. Stokkel1, Emma R. Mulder2, Otto S. Hoekstra2, Danielle J. Vugts2, Guus A.M.S. Van Dongen2, Henk M. Verheul2, Stefan Evers4, Jean J. L. Tessier3, Jose Saro4, Jan H.M. Schellens1,5 and C. Willemien Menke-van der Houven van Oordt2

1The Netherlands Cancer Institute, Amsterdam, The Netherlands

2VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands

3Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland

4Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland

5Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands

6Centre for Human Drug Research, Leiden, The Netherlands

Correspondence to:

C. Willemien Menke-van der Houven van Oordt, email: c.menke@vumc.nl

Keywords: immunocytokine; interleukin-2; 89Zr; biodistribution; immuno-PET

Received: March 24, 2018     Accepted: April 21, 2018     Published: May 15, 2018

ABSTRACT

Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) α 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.


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