KEY PUBLICATIONS

Gelonin Sequence

1: Rosenblum MG, Kohr WA, Beattie KL, Beattie WG, Marks W, Toman PD, Cheung L.

Amino acid sequence analysis, gene construction, cloning, and expression of gelonin, a toxin derived from Gelonium multiflorum.
J Interferon Cytokine Res. 1995 Jun;15(6):547-55.

Hum195/rGel for treatment of AML and Myelodysplastic Syndrome (MDS):

1: Duzkale H, Pagliaro LC, Rosenblum MG, Varan A, Liu B, Reuben J, Wierda WG, Korbling M, McMannis JD, Glassman AB, Scheinberg DA, Freireich EJ.

Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel.
Biol Blood Marrow Transplant. 2003 Jun;9(6):364-72.

2: Pagliaro LC, Liu B, Munker R, Andreeff M, Freireich EJ, Scheinberg DA, Rosenblum MG.

Humanized M195 monoclonal antibody conjugated to recombinant gelonin: an anti-CD33 immunotoxin with antileukemic activity.
Clin Cancer Res. 1998 Aug;4(8):1971-6.

3: Xu Y, Xu Q, Rosenblum MG, Scheinberg DA.

Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice.
Leukemia. 1996 Feb;10(2):321-6.

4: McGraw KJ, Rosenblum MG, Cheung L, Scheinberg DA.

Characterization of murine and humanized anti-CD33, gelonin immunotoxins reactive against
myeloid leukemias.
Cancer Immunol Immunother. 1994 Dec;39(6):367-74.

Melanoma Treatment Products: ScFvMel/TNF-alpha, ScFvMel/rGel and ScFvMel/Granzyme

1: Kim S, Cheung LH, Zhang W, Rosenblum MG.

Improved expression of a soluble single chain antibody fusion protein containing tumor necrosis factor in Escherichia coli.                                                            Appl Microbiol Biotechnol. 2007 Nov;77(1):99-106. Epub 2007 Aug 17.

2: Liu Y, Zhang W, Cheung LH, Niu T, Wu Q, Li C, Van Pelt CS, Rosenblum MG.

The antimelanoma immunocytokine scFvMEL/TNF shows reduced toxicity and potent antitumor activity against human tumor xenografts.

Neoplasia. 2006 May;8(5):384-93.

3: Liu Y, Zhang W, Niu T, Cheung LH, Munshi A, Meyn RE Jr, Rosenblum MG.

Targeted apoptosis activation with GrB/scFvMEL modulates melanoma growth, metastatic spread, chemosensitivity, and radiosensitivity.

Neoplasia. 2006 Feb;8(2):125-35.

4: Liu Y, Cheung LH, Marks JW, Rosenblum MG.

Recombinant single-chain antibody fusion construct targeting human melanoma cells and containing tumor necrosis factor.
Int J Cancer. 2004 Feb 10;108(4):549-557. PMID: 14696119

5: Liu Y, Cheung LH, Hittelman WN, Rosenblum MG.

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. 2003 Dec;2(12):1341-50.

6: Rosenblum MG, Cheung LH, Liu Y, Marks JW 3rd.

Design, expression, purification, and characterization, in vitro and in vivo, of an antimelanoma single-chain Fv antibody fused to the toxin gelonin.
Cancer Res. 2003 Jul 15;63(14):3995-4002.

7: Rosenblum MG, Marks JW, Cheung LH.

Comparative cytotoxicity and pharmacokinetics of antimelanoma immunotoxins containing either natural or recombinant gelonin.
Cancer Chemother Pharmacol. 1999;44(4):343-8.

8: Rosenblum MG, Cheung L, Kim SK, Mujoo K, Donato NJ, Murray JL.

Cellular resistance to the antimelanoma immunotoxin ZME-gelonin and strategies to
target resistant cells.
Cancer Immunol Immunother. 1996 Feb;42(2):115-21.

9: Rosenblum MG, Cheung L, Mujoo K, Murray JL.

An antimelanoma immunotoxin containing recombinant human tumor necrosis factor: tissue disposition, pharmacokinetic, and therapeutic studies in xenograft models.
Cancer Immunol Immunother. 1995 May;40(5):322-8.

10: Mujoo K, Cheung L, Murray JL, Rosenblum MG.

Pharmacokinetics, tissue distribution, and in vivo antitumor effects of the antimelanoma immunotoxin ZME-gelonin.
Cancer Immunol Immunother. 1995 May;40(5):339-45.

11: Rosenblum MG, Murray JL, Cheung L, Rifkin R, Salmon S, Bartholomew R. Related Articles, Links

A specific and potent immunotoxin composed of antibody ZME-018 and the plant toxin gelonin.
Mol Biother. 1991 Mar;3(1):6-13.

Breast Cancer Treatment: Anti HER2 Compounds

1: Lyu MA, Kurzrock R, Rosenblum MG.

The immunocytokine scFv23/TNF targeting HER-2/neu induces synergistic cytotoxic effects with 5-fluorouracil in TNF-resistant pancreatic cancer cell lines.                  Biochem Pharmacol. 2008 Feb 15;75(4):836-46. Epub 2007 Oct 22.

2: Lyu MA, Rosenblum MG.

The immunocytokine scFv23/TNF sensitizes HER-2/neu-overexpressing SKBR-3 cells to tumor necrosis factor (TNF) via up-regulation of TNF receptor-1.

Mol Cancer Ther. 2005 Aug;4(8):1205-13.

3: Rosenblum MG, Horn SA, Cheung LH.

A novel recombinant fusion toxin targeting HER-2/NEU-over-expressing cells and containing human tumor necrosis factor.
Int J Cancer. 2000 Oct 15;88(2):267-73.

4: Rosenblum MG, Shawver LK, Marks JW, Brink J, Cheung L, Langton-Webster B.

Recombinant immunotoxins directed against the c-erb-2/HER2/neu oncogene product: in vitro cytotoxicity, pharmacokinetics, and in vivo efficacy studies in xenograft models.
Clin Cancer Res. 1999 Apr;5(4):865-74.

VEGF/rGel and VEGF/Granzyme B: Potentially Useful in Many Solid Tumors

1: Hsu AR, Cai W, Veeravagu A, Mohamedali KA, Chen K, Kim S, Vogel H, Hou LC, Tse V, Rosenblum MG, Chen X.

Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel.

J Nucl Med. 2007 Mar;48(3):445-54.

2: Kim S, Mohamedali KA, Cheung LH, Rosenblum MG.

Overexpression of biologically active VEGF121 fusion proteins in Escherichia coli.

J Biotechnol. 2007 Feb 20;128(3):638-47. Epub 2006 Dec 12.

3: Mohamedali KA, Poblenz AT, Sikes CR, Navone NM, Thorpe PE, Darnay BG, Rosenblum MG.

Inhibition of prostate tumor growth and bone remodeling by the vascular targeting agent VEGF121/rGel.

Cancer Res. 2006 Nov 15;66(22):10919-28.

4: Mohamedali KA, Kedar D, Sweeney P, Kamat A, Davis DW, Eve BY, Huang S, Thorpe PE, Dinney CP, Rosenblum MG.

The vascular-targeting fusion toxin VEGF121/rGel inhibits the growth of orthotopic human bladder carcinoma tumors.

Neoplasia. 2005 Oct;7(10):912-20.

5: Akiyama H, Mohamedali KA, E Silva RL, Kachi S, Shen J, Hatara C, Umeda N, Hackett SF, Aslam S, Krause M, Lai H, Rosenblum MG, Campochiaro PA.

Vascular targeting of ocular neovascularization with a vascular endothelial growth factor121/gelonin chimeric protein.

Mol Pharmacol. 2005 Dec;68(6):1543-50. Epub 2005 Sep 8.

6: Ran S, Mohamedali KA, Luster TA, Thorpe PE, Rosenblum MG.

The vascular-ablative agent VEGF(121)/rGel inhibits pulmonary metastases of MDA-MB-231 breast tumors.

Neoplasia. 2005 May;7(5):486-96.

7: Veenendaal LM, Jin H, Ran S, Cheung L, Navone N, Marks JW, Waltenberger J, Thorpe P, Rosenblum MG.

In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors.
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7866-71.

8: Liu Y, Cheung LH, Thorpe P, Rosenblum MG.

Mechanistic studies of a novel human fusion toxin composed of vascular endothelial growth factor (VEGF)121 and the serine protease granzyme B: directed apoptotic events in vascular endothelial cells.
Mol Cancer Ther. 2003 Oct;2(10):949-59. PMID: 14578460

Other Constructs

1. Martínez-Torrecuadrada JL, Cheung LH, López-Serra P, Barderas R, Cañamero M, Ferreiro S, Rosenblum MG, Casal JI.

Antitumor activity of fibroblast growth factor receptor 3-specific immunotoxins in a xenograft mouse model of bladder carcinoma is mediated by apoptosis.                 Mol Cancer Ther. 2008 Apr;7(4):862-73.

2: Lyu MA, Cheung LH, Hittelman WN, Marks JW, Aguiar RC, Rosenblum MG.

The rGel/BLyS fusion toxin specifically targets malignant B cells expressing the BLyS receptors BAFF-R, TACI, and BCMA.

Mol Cancer Ther. 2007 Feb;6(2):460-70. Epub 2007 Jan 31.

3: Nimmanapalli R, Lyu MA, Du M, Keating MJ, Rosenblum MG, Gandhi V.

The growth factor fusion construct containing B-lymphocyte stimulator (BLyS) and the toxin rGel induces apoptosis specifically in BAFF-R-positive CLL cells.

Blood. 2007 Mar 15;109(6):2557-64. Epub 2006 Nov 21.

4: Chu TC, Marks JW 3rd, Lavery LA, Faulkner S, Rosenblum MG, Ellington AD, Levy M.

Aptamer:toxin conjugates that specifically target prostate tumor cells.

Cancer Res. 2006 Jun 15;66(12):5989-92.

5: Mehta K, Ocanas L, Malavasi F, Marks JW, Rosenblum MG.

Retinoic acid-induced CD38 antigen as a target for immunotoxin-mediated killing of leukemia cells.

Mol Cancer Ther. 2004 Mar;3(3):345-52.

2008 AACR Scientific Posters (pdf)

(4056) Characterization studies of novel human anti-CEA immunotoxins containing rGel

Sehoon Kim, Lawrence H. Cheung, Weihe Zhang, K. Dane Wittrup and Michael G. Rosenblum. Immunopharmacology and Targeted Therapy Laboratory, Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, Texas, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.

(4055) The rGel/BLyS Fusion Toxin Inhibits Interleukin-6 Signaling via Down Interleukin-6 Receptor in Diffuse Large B Cell Lymphoma

Mi-Ae Lyu, Lawrence H.Cheung, John W. Marks, Ricardo C.T. Aguiar, and Michael G. Rosenblum.  Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, and Department of Medicine, UTHSC, San Antonio

2005 AACR Scientific Posters (pdf)

(4624) The vascular targeting agent VEGF121/rGel inhibits bone remodeling and skeletal metastases through a unique mechanism.

Khalid A. Mohamedali, Ann T. Poblenz, Chuck Sikes, Troy Luster, Nora Navone, Philip Thorpe, Bryant Darnay, Michael G. Rosenblum. UT M.D. Anderson Cancer Center, Houston, TX, UT Southwestern Medical Center, Dallas, TX

(1517) The growth factor toxin construct rGel/BLyS specifically targets tumor cells expressing BAFF-R, TACI, and BCMA.

Mi-Ae Lyu, Lawrence H. Cheung, John H. Marks, Walter N. Hittleman, Varsha V. Gandhi, and Michael G.
Rosenblum. Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston , TX 77030

(687) The anti-gp240 fusion toxin scFvMEL/TNF shows potent antitumor activity and synergy with chemotherapeutic agents.

Yuying Liu, Weihe Zhang, Lawrence H. Cheung, Qingping Wu, Chun Li, Michael G. Rosenblum. Department of Experimental Therapeutics and Experimental Diagnostic Imaging. M.D. Anderson Cancer Center, Houston , TX 77030

Recent Abstracts

2005 Association for Research in Vision and Ophthalmology Meeting

(455/B429) A VEGF121-Gelonin Fusion Protein
(VEGF121/rGel) Induces Regression of Subretinal and Choroidal Neovascularization (CNV)

AACR 2005 Meeting,  Anaheim, CA

Targeting PSMA on tumor cells using novel aptamer-gelonin conjugates.

Abstracts from AACR 2004 Meeting, Orlando FL
(Available / Combined in an Acrobat pdf)

Molecular mechanism of a synergistic interaction between scFv23/TNF and 5-Fluorouracil in L3.6pl
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/510-a

Vascular targeting with VEGF121/rGel inhibits angiogenesis:
Specific effects assessed using micro-array analysis
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/594-a

The vascular targeting agent, VEGF121/rGel, inhibits the growth of human MDA-MB-231 breast tumors in the lungs of SCID mice
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/693-c

Development of "designer toxins" with reduced antigenicity and size
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/874-c

Targeted delivery granzyme B to melanoma cells: Directed apoptotic effects, anti-tumor activity and synergy with chemotherapeutic agents
http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/875-b

Abstracts from AACR 2003 Meeting, Washington, D.C.
(Available / Combined in an Acrobat pdf)

VEGF121 gelonin fusion protein inhibits breast cancer metastasis in nude mice.
(pdf)

In vitro and in vivo anti-angiogenic effects of VEGF121/rGel fusion toxin.
(pdf)

A unique fusion construct GrB/scFvMEL capable of targeted delivery of human pro-apoptotic granzyme B to human melanoma cells.
(pdf)

The anti-melanoma fusion toxin scFvMEL/TNF has a unique cytotoxic mechanism of action and delivers TNF to human tumor xenografts.
(pdf)

Targeting human pancreatic cancer cells with the anti-HER-2 fusion toxin scFv23/TNF.
(pdf)

In-vitro studies comparing the recombinant, single-chain immunotoxins scFv23/rGel and ML3.9/rGel which recognize the HER2/neu proto-oncogene.
(pdf)

Phase I clinical trial of the anti-CD-33 immunotoxin HuM195/rGel
(pdf)