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Klein C, Waldhauer I, Nicolini VG, et al. Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines. Oncoimmunology. 2017;6(3):e1277306doi: 10.1080/2162402X.2016.1277306.
Klein, C., Waldhauer, I., Nicolini, V. G., Freimoser-Grundschober, A., Nayak, T., Vugts, D. J., Dunn, C., Bolijn, M., Benz, J., Stihle, M., Lang, S., Roemmele, M., Hofer, T., van Puijenbroek, E., Wittig, D., Moser, S., Ast, O., Brünker, P., Gorr, I. H., Neumann, S., de Vera Mudry, M. C., Hinton, H., Crameri, F., Saro, J., Evers, S., Gerdes, C., Bacac, M., van Dongen, G., Moessner, E., & Umaña, P. (2017). Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines. Oncoimmunology, 6(3), e1277306. https://doi.org/10.1080/2162402X.2016.1277306
Klein, Christian, et al. "Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines." Oncoimmunology vol. 6,3 (2017): e1277306. doi: https://doi.org/10.1080/2162402X.2016.1277306
Klein C, Waldhauer I, Nicolini VG, Freimoser-Grundschober A, Nayak T, Vugts DJ, Dunn C, Bolijn M, Benz J, Stihle M, Lang S, Roemmele M, Hofer T, van Puijenbroek E, Wittig D, Moser S, Ast O, Brünker P, Gorr IH, Neumann S, de Vera Mudry MC, Hinton H, Crameri F, Saro J, Evers S, Gerdes C, Bacac M, van Dongen G, Moessner E, Umaña P. Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines. Oncoimmunology. 2017 Jan 11;6(3):e1277306. doi: 10.1080/2162402X.2016.1277306. eCollection 2017. PMID: 28405498; PMCID: PMC5384349.
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Oncoimmunology. 2017 Jan 11;6(3):e1277306. doi: 10.1080/2162402X.2016.1277306. eCollection 2017.

Cergutuzumab amunaleukin (CEA-IL2v), a CEA-targeted IL-2 variant-based immunocytokine for combination cancer immunotherapy: Overcoming limitations of aldesleukin and conventional IL-2-based immunocytokines.

Oncoimmunology

Christian Klein, Inja Waldhauer, Valeria G Nicolini, Anne Freimoser-Grundschober, Tapan Nayak, Danielle J Vugts, Claire Dunn, Marije Bolijn, Jörg Benz, Martine Stihle, Sabine Lang, Michaele Roemmele, Thomas Hofer, Erwin van Puijenbroek, David Wittig, Samuel Moser, Oliver Ast, Peter Brünker, Ingo H Gorr, Sebastian Neumann, Maria Cristina de Vera Mudry, Heather Hinton, Flavio Crameri, Jose Saro, Stefan Evers, Christian Gerdes, Marina Bacac, Guus van Dongen, Ekkehard Moessner, Pablo Umaña

Affiliations

  1. Roche Pharma Research & Early Development, Roche Innovation Center Zurich , Schlieren, Switzerland.
  2. Roche Pharma Research & Early Development, Roche Innovation Center Basel , Basel, Switzerland.
  3. Roche Pharma Research & Early Development, Department of Radiology & Nuclear Medicine, VU University Medical Center , Amsterdam, the Netherlands.
  4. Roche Pharma Research & Early Development, Roche Innovation Center Munich , Penzberg, Germany.

PMID: 28405498 PMCID: PMC5384349 DOI: 10.1080/2162402X.2016.1277306

Abstract

We developed cergutuzumab amunaleukin (CEA-IL2v, RG7813), a novel monomeric CEA-targeted immunocytokine, that comprises a single IL-2 variant (IL2v) moiety with abolished CD25 binding, fused to the C-terminus of a high affinity, bivalent carcinoembryonic antigen (CEA)-specific antibody devoid of Fc-mediated effector functions. Its molecular design aims to (i) avoid preferential activation of regulatory T-cells vs. immune effector cells by removing CD25 binding; (ii) increase the therapeutic index of IL-2 therapy by (a) preferential retention at the tumor by having a lower dissociation rate from CEA-expressing cancer cells vs. IL-2R-expressing cells, (b) avoiding any FcγR-binding and Fc effector functions and (c) reduced binding to endothelial cells expressing CD25; and (iii) improve the pharmacokinetics, and thus convenience of administration, of IL-2. The crystal structure of the IL2v-IL-2Rβγ complex was determined and CEA-IL2v activity was assessed using human immune effector cells. Tumor targeting was investigated in tumor-bearing mice using

Keywords: Antibody; CEA; CEACAM5; IL-2; IL2v; Immunocytokine

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