Targeting Interleukin-4 Receptor α with Hybrid Peptide for Effective Cancer Therapy

Molecular Cancer Therapeutics - Tập 11 Số 1 - Trang 235-243 - 2012
Liying Yang1,2, Tomohisa Horibe1,2, Masayuki Kohno1, Mari Haramoto1,2, Koji Ohara1,2, Raj K. Puri1,2, Koji Kawakami1,2
1Authors' Affiliations: 1Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto; 2Upstream Infinity, Inc., 1-7-8 Kaigan, Minato-ku, Tokyo, Japan; and 3Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US food and Drug Administration, Bethesda, Maryland
2Upstream Infinity, Inc., 1-7-8 Kaigan, Minato-ku, Tokyo, Japan

Tóm tắt

Abstract Interleukin-4 receptor α (IL-4Rα) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Rα–lytic peptide that targets the IL-4Rα chain. The IL-4Rα–lytic peptide contains a target moiety to bind to IL-4Rα and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL-4Rα–lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Rα–lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Rα, determined by quantitative real-time PCR. The IC50 ratios of the lytic peptide to the IL-4Rα–lytic peptide correlated well with the expression levels of IL-4Rα on cancer cells (r = 0.80). In addition, IL-4Rα–lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Rα–lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Rα–positive solid cancers. Mol Cancer Ther; 11(1); 235–43. ©2011 AACR.

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Tài liệu tham khảo

Pastan, 1997, Targeted therapy of cancer with recombinant immunotoxins, Biochimica et Biophysica Acta, 1333, C1

Kreitman, 2005, Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies, J Clin Oncol, 23, 6719, 10.1200/JCO.2005.11.437

Rand, 2000, Intratumoral administration of recombinant circularly permuted interleukin-4-pseudomonas exotoxin in patients with high-grade glioma, Clin Cancer Res, 6, 2157

Schnell, 2002, A phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma, Clin Cancer Res, 8, 1779

Kawakami, 2006, Targeted anticancer immunotoxins and cytotoxic agents with direct killing moieties, ScientificWorldJournal, 6, 781, 10.1100/tsw.2006.162

Kreitman, 2006, Immunotoxins for targeted cancer therapy, AAPS J, 8, E532, 10.1208/aapsj080363

Olsen, 2001, Pivotal phase III trial of two levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma, J Clin Oncol, 19, 376, 10.1200/JCO.2001.19.2.376

Kreitman, 2000, Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies, J Clin Oncol, 18, 1622, 10.1200/JCO.2000.18.8.1622

Tsutsumi, 2000, Site-specific chemical modification with polyethylene glycol of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) improves antitumor activity and reduces animal toxicity and immunogenicity, Proc Natl Acad Sci U S A, 97, 8548, 10.1073/pnas.140210597

Melani, 1998, Targeting of interleukin 2 to human ovarian carcinoma by fusion with a single-chain Fv of antifolate receptor antibody, Cancer Res, 58, 4146

Kohno, 2011, A novel hybrid peptide targeting EGFR-expressing cancers, Eur J Cancer, 47, 773, 10.1016/j.ejca.2010.10.021

Ellerby, 1999, Anti-cancer activity of targeted pro-apoptotic peptides, Nat Med, 5, 1032, 10.1038/12469

Papo, 2003, A novel lytic peptide composed of DL-amino acids selectively kills cancer cells in culture and mice, J Biol Chem, 278, 21018, 10.1074/jbc.M211204200

Obiri, 1993, Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4, J Clin Invest, 91, 88, 10.1172/JCI116205

Obiri, 1994, Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells, Clin Exp Immunol, 95, 148, 10.1111/j.1365-2249.1994.tb06029.x

Leland, 2000, Human breast carcinoma cells express type II IL-4 receptors and are sensitive to antitumor activity of a chimeric IL-4-Pseudomonas exotoxin fusion protein in vitro and in vivo, Mol Med, 6, 165, 10.1007/BF03402112

Kioi, 2005, Expression and targeting of interleukin-4 receptor for primary and advanced ovarian cancer therapy, Cancer Res, 65, 8388, 10.1158/0008-5472.CAN-05-1043

Puri, 1994, Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein, Int J Cancer, 58, 574, 10.1002/ijc.2910580421

Husain, 1997, Interleukin-4 receptor expression on AIDS-associated Kaposi's sarcoma cells and their targeting by a chimeric protein comprised of circularly permuted interleukin-4 and Pseudomonas exotoxin, Mol Med, 3, 327, 10.1007/BF03401811

Kawakami, 2000, Structure, function, and targeting of interleukin 4 receptors on human head and neck cancer cells, Cancer Res, 60, 2981

Weber, 2003, Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma, J Neuro-Oncol, 64, 125, 10.1007/BF02700027

Garland, 2005, Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor, J immunother, 28, 376, 10.1097/01.cji.0000162782.86008.mL

Beseth, 2004, Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts, Ann Thorac Surg, 78, 436, 10.1016/j.athoracsur.2004.03.010

Russell, 1993, Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor, Science, 262, 1880, 10.1126/science.8266078

Kondo, 1993, Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4, Science, 262, 1874, 10.1126/science.8266076

Murata, 1997, Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells, Biochem Biophys Res Commun, 238, 90, 10.1006/bbrc.1997.7248

Obiri, 1995, Receptor for interleukin 13 interaction with interleukin 4 by a mechanism that does not involve the common gamma chain shared by receptors for interleukins 2, 4, 7, 9, and 15, J Biol Chem, 270, 8797, 10.1074/jbc.270.15.8797

Murata, 1998, Interleukin-13 receptor alpha' but not alpha chain: a functional component of interleukin-4 receptors, Blood, 91, 3884, 10.1182/blood.V91.10.3884

Park, 2006, Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3-kinase inhibition in the human cervical cancer cell line, Cancer Res Treat, 38, 112, 10.4143/crt.2006.38.2.112

Wang, 1997, A mixed-charge pair in human interleukin 4 dominates high-affinity interaction with the receptor α chain, Proc Natl Acad Sci USA, 94, 1657, 10.1073/pnas.94.5.1657

Mueller, 2002, Structure, binding, and antagonists in the IL-4/IL-13 receptor system, Biochim Biophys Acta, 1592, 237, 10.1016/S0167-4889(02)00318-X

Hage, 1999, Crystal structure of the interleukin-4/receptor α chain complex reveals a mosaic binding interface, Cell, 97, 271, 10.1016/S0092-8674(00)80736-9

Yao, 2005, Identification of core functional region of murine IL-4 using peptide phage display and molecular modeling, Int Immuno, 18, 19, 10.1093/intimm/dxh338

Chen, 1997, Effects of the anti-bacterial peptide cecropin B and its analogs, cecropins B-1 and B-2, on liposomes, bacteria, and cancer cells, Biochimica et Biophysica Acta, 1336, 171, 10.1016/S0304-4165(97)00024-X

Baker, 1993, Anticancer efficacy of Magainin2 and analogue peptides, Cancer Res, 53, 3052

Hoskin, 2008, Studies on anticancer activities of antimicrobial peptides, Biochimica et Biophysica Acta, 1778, 357, 10.1016/j.bbamem.2007.11.008

Shai, 1999, Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides, Biochimica et Biophysica Acta, 1462, 55, 10.1016/S0005-2736(99)00200-X

Papo, 2003, New lytic peptides based on the D, L-amphipathic helix motif preferentially kill tumor cells compared to normal cells, Biochemistry, 42, 9346, 10.1021/bi027212o

Utsugi, 1991, Elevated expression of phosphatidylserine in the outer membrane leaflet of human tumor cells and recognition by activated human blood monocytes, Cancer Res, 51, 3062

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Molecular Cancer Therapeutics

Tập 11 Số 1

235-243

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