Antitumor effect of MCC-465, pegylated liposomal doxorubicin tagged with newly developed monoclonal antibody GAH, in colorectal cancer xenografts
Tetsuya Hamaguchi
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorCorresponding Author
Yasuhiro Matsumura
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Investigative Treatment Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa 277-8577
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorYukihiro Nakanishi
Department of Pathology, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorKei Muro
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorYasuhide Yamada
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorYasuhiro Shimada
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorKuniaki Shirao
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorHisae Niki
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorSaiko Hosokawa
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorToshiaki Tagawa
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorTadao Kakizoe
President, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorTetsuya Hamaguchi
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorCorresponding Author
Yasuhiro Matsumura
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Investigative Treatment Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa 277-8577
To whom correspondence should be addressed. E-mail: [email protected]Search for more papers by this authorYukihiro Nakanishi
Department of Pathology, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorKei Muro
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorYasuhide Yamada
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorYasuhiro Shimada
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorKuniaki Shirao
Department of Medicine, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorHisae Niki
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorSaiko Hosokawa
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorToshiaki Tagawa
Pharmaceutical Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033
Search for more papers by this authorTadao Kakizoe
President, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
Search for more papers by this authorAbstract
MCC-465 is an immunoliposome-encapsulated doxorubicin. The liposome is tagged with polyethylene glycol and the F(ab)2 of a monoclonal antibody named GAH, a human antibody obtained by the hybridoma technique. The epitope recognized by GAH is not well characterized, but human gastric, colorectal, and mammary cancer cells were GAH-positive, while the normal counterparts were GAH-negative. Pegylated liposome doxorubicin (PLD) and MCC-465 did not show significant antitumor activity against GAH-negative Caco-2 xenografts. On the other hand, MCC-465 exhibited significantly superior antitumor effects against GAH-positive WiDr-Tc and SW837 xenografts, compared with PLD. Immunohis-tochemistry with GAH revealed that 94% (100 of 106) of surgical specimens of colorectal cancer were GAH-positive. These results warrant a phase I clinical trial of MCC-465 for patients with metastatic colorectal cancer.
References
- 1 Cancer Statistics in Japan '03. http://www.ncc.go.jp/en/statistics/2003/index.html.
- 2 Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 1965; 13: 238–52.
- 3 Allen TM, Hansen C, Martin F, Redemann C, Yau-young A. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim- Biophys Acta 1991; 1066: 29–36.
- 4 Maruyama K, Yuda T, Okamoto A, Kojima S, Suginaka A, Iwatsuru M. Prolonged circulation time in vivo of large unilamellar liposomes composed of distearoyl phosphatidylcholine and cholesterol containing amphipathic poly(ethylene glycol). Biochim. Biophys Acta 1992; 1128: 44–9.
- 5 Gabizon A, Catane R, Uziely B, Kafman B, Safra T, Cohen R, Martin F, Huang A, Balenholz Y. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-gly-col coated liposomes. Cancer Res 1994; 54: 987–92.
- 6 Northfelt DW, Martin FJ, Working P, Volberding PA, Rusell J, Newman M, Amantea MA, Kaplan LD. Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma. J Clin Pharmacol 1996; 36: 55–63.
- 7 Koukourakis MI, Koukourak S, Giatromanolaki A, Archimandrites SC, Skarlatos J, Beroukas K, Bizakis JG, Retails G, Karkavitsas N, Helidonis ES. Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small cell lung cancer and head and neck cancer. J Clin Oncol 1999; 17: 3512–21.
- 8 Harrington KJ, Mohammadtaghi S, Uster PS, Glass D, Peters AM, Vile RG, Stewart JSW. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled pegylated liposomes. Clin Cancer Res 2001; 7: 243–54.
- 9 Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumour agent smancs. Cancer Res 1986; 46: 6387–92.
- 10 Maeda H, Matsumura Y. Tumoritropic and lymphotropic principles of macromolecular drugs. Crit Rev Ther Drug Carrier Syst 1989; 6: 193–210.
- 11 Muggia FM. Doxorubicin-polymer conjugates: further demonstration of the concept of enhanced permeability and retention. Clin Cancer Res 1999; 5: 7–8.
- 12 Hosokawa S, Tagawa T, Niki H, Hirakawa Y, Nohga K, Nagaike K. Efficacy of immunoliposomes in cancer models in a cell-surface-antigen-density-dependent manner. Br J Cancer 2003; 89: 1545–51.
- 13 Aamdal S, Fodstad O, Nesland JM, Pihl A. Characteristic of human tumor xenografts transplanted under the renal capsule of immunocompetent mice. Br J Cancer 1985; 51: 347–56.
- 14 Jain RK. Understanding barriers to drug delivery: high resolution in vivo imaging is key. Clin Cancer Res 1999; 5: 1605–6.
- 15 Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol 1993; 11: 1573–82.
- 16 Safra T, Muggia F, Jeffers S, Tsao-Wei DD, Groshen S, Lyass O, Henderson R, Berry G, Gabizon A. Pegylated liposomal doxorubicin (Doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Ann Oncol 2000; 11: 1029–33.
- 17 Northfelt DW, Dezube BJ, Thommes JA, Miller BJ, Fischl MA, Friedman-Kien A, Kaplan LD, Du Mond C, Mamelok RD, Henry DH. Pegylated-lipo-somal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. J Clin Oncol 1998; 16: 2445–51.
- 18 Stewart S, Jablonowski H, Goebel FD, Arasteh K, Spittle M, Rios A, Aboulafia D, Galleshaw J, Dezube BJ. Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group. J Clin Oncol 1998; 16: 683–91.
- 19 Toma S, Tucci A, Villani G, Carteni G, Spadini N, Palumbo R. Liposomal doxorubicin (Caelyx) in advanced pretreated soft tissue sarcomas: a phase II study of the Italian Sarcoma Group (ISO). Anticancer Res 2000; 20: 485–91.
- 20 Judson I, Radford JA, Harris M, Bay J-Y, van Hoesel Q, le Cesne A, van Oosterom AT, Demons MJ, Kamby C, Hermans C, Whittaker J, Donato di Paola E, Verweij J, Nielsen S. Randomized phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2001; 37: 870–7.
- 21 Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, Roman L, Uziely B, Muderspach L, Garcia A, Burnett A, Greco FA, Morrow CP, Paradiso LJ, Liang L-J. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol 1997; 15: 987–93.
- 22 Markman M, Kennedy A, Webster K, Peterson G, Kulp B, Belinson J. Phase 2 trial of liposomal doxorubicin (40 mg/m2) in platinum/paclitaxel-refrac-tory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 2000; 78: 369–72.
- 23 Gordon AN, Granai CO, Rose PG, Hainsworth J, Lopez A, Weissman C, Resales R, Sharpington T. Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer. J Clin Oncol 2000; 18: 3093–100.
- 24 Ranson MR, Carmicheal J, O'Byme K, Stewart S, Smith D, Howell, A. Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. J Clin Oncol 1998; 15: 3185–91.
- 25 Shields AF, Lange LM, Zalupski MM. Phase II study of liposomal doxorubicin in patients with advanced colorectal cancer. Am J Clin Oncol 2001; 24: 96–8.
- 26 Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderso IC, Norton L. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overex-pressing metastatic breast cancer. J Clin Oncol 1996; 14: 737–44.
- 27 Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. N Engl J Med 2001; 344: 783–92.
- 28 MclLaughlin P, Grillo-Lopez A, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas VF, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to four-dose treatment program. J Clin Oncol 1998; 16: 2825–33.
- 29 Czuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBugllo AF, Jonas C, Kllppenstein D, Dallaire B, Yarns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 1999; 17: 268–76.
- 30 Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, van den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235–42.
- 31 Suzuki S, Inoue K, Hongoh A, Hashimoto Y, Yamazoe Y. Modulation of doxorubicin resistance in a doxorubicin-resistant human leukaemia cell by an immunoliposome targeting transferrin receptor. Br J Cancer 1997; 76: 83–9.
