FUSION PROTEINS WITH TOXIC ACTIVITY - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 259

of anti-CD19 and anti-CD22 immunotoxins (Combotox) in
adult patients with refractory B-lineage acute lymphoblastic
leukaemia. Br. J. Haematol. 154(4), 471-476.
35. Vitetta ES. (2000) Immunotoxins and vascular leak syndrome.
Cancer J. 6(Suppl. 3), S218-S224.
36. Ortiz-Sanchez E, Helguera G, Daniels TR, Penichet ML.
(2008) Antibody-cytokine fusion proteins: applications in
cancer therapy. Expert Opin. Biol. Ther. 8, 609-632.
37. Rainov NG, Soling A. (2006) Clinical studies with targeted
toxins in malignant glioma. Rev. Recent Clin. Trials 1(2),
119-131.
38. Gillies SD, Lan Y, Hettmann T, Brunkhorst B, Sun Y,
Mueller SO, et al. (2011) A low-toxicity IL-2-based
immunocytokine retains antitumor activity despite its
high degree of IL-2 receptor selectivity. Clin. Cancer
Res. 17(11), 3673-3685.
39. Shi M, Zhang L, Gu H-T, Jiang F-Q, Qian L, Yu M, et al.
(2007) Efficient growth inhibition of ErbB2-overexpressing
tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein
in vitro and in vivo. Acta Pharmacol. Sin. 28(10), 1611-1620.
40. Shusterman S, London WB, Gillies SD, Hank JA, Voss SD,
Seeger RC, et al. (2010) Antitumor activity of hu14.18-IL2 in
patients with relapsed/refractory neuroblastoma: a children's
oncology group (COG) phase II study. J. Clin. Oncol. 28(33),
4969-4975.
41. Williams P, Galipeau J. (2011) GM-CSF-based fusion
cytokines as ligands for immune modulation. J. Immunol.
186(10), 5527-5532.
42. Lechner MG, Russell SM, Bass RS, Epstein AL. (2011)
Chemokines, costimulatory molecules and fusion proteins
for the immunotherapy of solid tumors. Immunotherapy
3(11), 1317-1340.
43. Andrady C, Sharma SK, Chester KA. (2011) Antibody-
enzyme fusion proteins for cancer therapy. Immunotherapy
3(2), 193-211.
44. Tur MK, Neef I, Jager G, Teubner A, Stocker M, Melmer G,
et al. (2009) Immunokinases, a novel class of immuno-
therapeutics for targeted cancer therapy. Curr. Pharm. Des.
15(23), 2693-2699.
45. De Lorenzo C, Di Malta C, Cal ı G, Troise F, Nitsch L,
D'Alessio G. (2007) Intracellular route and mechanism of
action of ERB-hRNase, a human anti-ErbB2 anticancer
immunoagent. FEBS Lett. 581(2), 296-300.
46. Krauss J, Arndt MAE, Vu BK, Newton DL, Rybak SM.
(2005) Targeting malignant B-cell lymphoma with a
humanized anti-CD22 scFv-angiogenin immunoenzyme.
Br. J. Haematol. 128(5), 602-609.
47. Krauss J, Arndt MAE, Vu BK, Newton DL, Seeber S, Rybak
SM. (2005) Efficient killing of CD22 þ tumor cells by a
humanized diabody-RNase fusion protein. Biochem. Biophys.
Res. Commun. 331(2), 595-602.
48. Rybak SM, Arndt MAE, Schirrmann T, Dubel S, Krauss J.
(2009) Ribonucleases and immunoRNases as anticancer
drugs. Curr. Pharm. Des. 15(23), 2665-2675.
49. Jia L-T, Zhang L-H, Yu C-J, Zhao J, Xu Y-M, Gui J-H, et al.
(2003) Specific

proapoptotic protein consisting of HER2 antibody and
constitutively active caspase-3. Cancer Res. 63(12),

3257-3262.
50. Yarkoni S, Kaminitz A, Sagiv Y, Askenasy N. (2010) Target-
ing of IL-2 receptor with a caspase fusion protein disrupts
autoimmunity in prediabetic and diabetic NOD mice.
Diabetologia 53(2), 356-368.
51. Sagiv Y, Kaminitz A, Lorberboum-Galski H, Askenasy N,
Yarkoni S. (2009) A fusion protein composed of IL-2 and
caspase-3 ameliorates the outcome of experimental inflam-
matory colitis. Ann. N. Y. Acad. Sci. 1173, 791-797.
52. Wang L-F, Zhou Y, Xu Y-M, Qiu X-C, Zhou B-G, Wang F,
et al. (2009) A caspase-6 and anti-HER2 antibody chimeric
tumor-targeted proapoptotic molecule decreased metastasis
of human osteosarcoma. Cancer Invest. 27(7), 774-780.
53. Xu Y-M, Wang L-F, Jia L-T, Qiu X-C, Zhao J, Yu C-J, et al.
(2004) A caspase-6 and anti-human epidermal growth factor
receptor-2 (HER2) antibody chimeric molecule suppresses
the growth of HER2-overexpressing tumors. J. Immunol.
173(1), 61-67.
54. Zhao J, Zhang L-H, Jia L-T, Zhang L, Xu Y-M, Wang Z, et al.
(2004) Secreted antibody/granzyme B fusion protein
stimulates selective killing of HER2-overexpressing tumor
cells. J. Biol. Chem. 279(20), 21343-21348.
55. Liu Y, Cheung LH, Hittelman WN, Rosenblum MG. (2003)
Targeted delivery of human pro-apoptotic enzymes to
tumor cells: in vitro studies describing a novel class of
recombinant highly cytotoxic agents. Mol. Cancer Ther.
2(12), 1341-1350.
56. Rosenblum MG, Barth S. (2009) Development of novel,
highly cytotoxic fusion constructs containing granzyme B:
unique mechanisms and functions. Curr. Pharm. Des. 15(23),
2676-2692.
57. Philpott GW, Bower RJ, Parker KL, Shearer WT, Parker CW.
(1974) Affinity cytotoxicity of tumor cells with antibody-
glucose oxidase conjugates, peroxidase, and arsphenamine.
Cancer Res. 34(9), 2159-2164.
58. Bagshawe KD. (1987) Antibody directed enzymes revive
anti-cancer prodrugs concept. Br. J. Cancer 56(5), 531-532.
59. Kogelberg H, Tolner B, Sharma SK, Lowdell MW, Qureshi U,
Robson M, et al. (2007) Clearance mechanism of a manno-
sylated antibody-enzyme fusion protein used in experimental
cancer therapy. Glycobiology 17(1), 36-45.
60. Bagshawe KD, Sharma SK, Begent RHJ. (2004) Antibody-
directed enzyme prodrug therapy (ADEPT)

for cancer.

Expert Opin. Biol. Ther. 4(11), 1777-1789.
61. Harding FA, Liu AD, Stickler M, Razo OJ, Chin R, Faravashi
N, et al. (2005) A beta-lactamase with reduced immunoge-
nicity for the targeted delivery of chemotherapeutics using
antibody-directed enzyme prodrug therapy. Mol. Cancer
Ther. 4(11), 1791-1800.
62. Schellmann N, Deckert PM, Bachran D, Fuchs H, Bachran C.
(2010) Targeted enzyme prodrug therapies. Mini Rev. Med.
Chem. 10(10), 887-904.
63. Wojcik T, Kiec-Kononowicz K. (2008) Catalytic activity of
certain antibodies as a potential tool for drug synthesis and

tumoricidal activity of a secreted