Antibody-Based Delivery of IL2 and Cytotoxics Eradicates Tumors in Immunocompetent Mice

被引：26

作者：

Gutbrodt, Katrin L. ^{[1
]}

Casi, Giulio ^{[2
]}

Neri, Dario ^{[1
]}

机构：

[1] ETH, Dept Chem & Appl Biosci, CH-8093 Zurich, Switzerland

[2] Philochem AG, Otelfingen, Switzerland

来源：

MOLECULAR CANCER THERAPEUTICS | 2014年 / 13卷 / 07期

基金：

瑞士国家科学基金会;

关键词：

IMMUNOCYTOKINE; VASCULATURE; INTERLEUKIN-2; CHALLENGES; CONJUGATE; DOMAIN;

D O I：

10.1158/1535-7163.MCT-14-0105

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Antibody-drug conjugates are increasingly being used for cancer therapy, but little is known about their ability to promote anticancer immunity, which may lead to long-lasting remissions. We investigated the therapeutic effect of antibody-based pharmacodelivery of cemadotin, a cytotoxic drug, and IL2, a strong proinflammatory cytokine. Using the F8 antibody, which selectively localizes to the tumor neovasculature, combination treatment led to tumor eradication, in a process dependent on CD8(+) T cells and natural killer cells in the C1498 syngeneic mouse model of acute myelogenous leukemia. The clinical combination of antibody-drug conjugates and antibody-cytokine proteins should be facilitated by their orthogonal toxicity profiles. (C) 2014 AACR.

引用

页码：1772 / 1776

页数：5

共 20 条

[1]

Targeted delivery of tumor necrosis factor-α to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin [J].

Balza, E ;

Mortara, L ;

Sassi, F ;

Monteghirfo, S ;

Carnemolla, B ;

Castellani, P ;

Neri, D ;

Accolla, RS ;

Zardi, L ;

Borsi, L .

CLINICAL CANCER RESEARCH, 2006, 12 (08) :2575-2582

[2]

Site-specific chemical modification of antibody fragments using traceless cleavable linkers [J].

Bernardes, Goncalo J. L. ;

Steiner, Martina ;

Hartmann, Isabelle ;

Neri, Dario ;

Casi, Giulio .

NATURE PROTOCOLS, 2013, 8 (11) :2079-2089

[3]

A Traceless Vascular-Targeting Antibody-Drug Conjugate for Cancer Therapy [J].

Bernardes, Goncalo J. L. ;

Casi, Giulio ;

Truessel, Sabrina ;

Hartmann, Isabelle ;

Schwager, Kathrin ;

Scheuermann, Joerg ;

Neri, Dario .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (04) :941-944

[4]

Selective targeting of tumoral vasculature: Comparison of different formats of an antibody (L19) to the ED-B domain of fibronectin [J].

Borsi, L ;

Balza, E ;

Bestagno, M ;

Castellani, P ;

Carnemolla, B ;

Biro, A ;

Leprini, A ;

Sepulveda, J ;

Burrone, O ;

Neri, D ;

Zardi, L .

INTERNATIONAL JOURNAL OF CANCER, 2002, 102 (01) :75-85

[5]

The Immunocytokine F8-IL2 Improves the Therapeutic Performance of Sunitinib in a Mouse Model of Renal Cell Carcinoma [J].

Frey, Katharina ;

Schliemann, Christoph ;

Schwager, Kathrin ;

Giavazzi, Raffaella ;

Johannsen, Manfred ;

Neri, Dario .

JOURNAL OF UROLOGY, 2010, 184 (06) :2540-2548

[6]

Antibody drug-conjugates targeting the tumor vasculature Current and future developments [J].

Gerber, Hans-Peter ;

Senter, Peter D. ;

Grewal, Iqbal S. .

MABS, 2009, 1 (03) :247-253

[7]

Antibody-Based Delivery of Interleukin-2 to Neovasculature Has Potent Activity Against Acute Myeloid Leukemia [J].

Gutbrodt, Katrin L. ;

Schliemann, Christoph ;

Giovannoni, Leonardo ;

Frey, Katharina ;

Pabst, Thomas ;

Klapper, Wolfram ;

Berdel, Wolfgang E. ;

Neri, Dario .

SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (201)

[8]

The antibody-based targeted delivery of interleukin-4 and 12 to the tumor neovasculature eradicates tumors in three mouse models of cancer [J].

Hemmerle, Teresa ;

Neri, Dario .

INTERNATIONAL JOURNAL OF CANCER, 2014, 134 (02) :467-477

[9]

Phase 0 Microdosing PET Study Using the Human Mini Antibody F16SIP in Head and Neck Cancer Patients [J].

Heuveling, Derrek A. ;

de Bree, Remco ;

Vugts, Danielle J. ;

Huisman, Marc C. ;

Giovannoni, Leonardo ;

Hoekstra, Otto S. ;

Leemans, C. Rene ;

Neri, Dario ;

van Dongen, Guus A. M. S. .

JOURNAL OF NUCLEAR MEDICINE, 2013, 54 (03) :397-401

[10]

Paclitaxel and immune system [J].

Javeed, Aqeel ;

Ashraf, Muhammad ;

Riaz, Amjad ;

Ghafoor, Aamir ;

Afzal, Sheryar ;

Mukhtar, Muhammad Mahmood .

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2009, 38 (04) :283-290

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