CBER Expertise
Development of Safe and Effective Tumor Vaccines and Gene Therapy products
Principal Investigator: Raj K. Puri, MD, PhD
Office / Division / Lab: OCTGT / DCGT / TVBB
Overview
Public Health Issue: Cancer is one of the most difficult public health problems. More than 1.4 million new cases will be diagnosed with cancer by end of the year 2008 and approximately 43% of them will die from this dreadful disease. Despite enormous efforts towards finding a cure and progress in some subsets, overall survival of cancer patients has not increased and new therapeutic approaches are warranted. A number of targeted gene therapy, therapeutic tumor vaccines and immunotherapy products are being developed over the past two to three decades.
Regulatory Contribution: Numerous investigational cancer gene therapies, tumor vaccines and immunotherapy products from industry, National Cancer Institute, and academic institutions are being reviewed at the FDA. However, to date, none of these products are in clinical use. The main impediment to successful product development is a lack of understanding of the biology of tumors, availability of appropriate tests for identity and potency of products, animal models to evaluate activity of these promising approaches and monitoring of tumor responses in patients.
Research Approach: This research program has been focused on the understanding of tumor characteristics and identification of potential tumor-associated cell surface proteins including hormone receptors that can be used to target novel therapeutic agents and also establish identity and potency of tumor vaccines. In addition, various animal models of human cancer have been established that are being used to evaluate safety and efficacy of tumor vaccines and gene therapy products. Genomics, a novel medical technology, is being used in the characterization of cellular tumor vaccines, stem cells and cell substrates that are used to manufacture cellular and gene therapy products and also identification of cancer stem cells in head and neck and brain tumors. As genomics technology provides analysis of the total genes expressed by a sample of total RNA, it provides a unique opportunity to identify the molecular signature of whole tumor, stem cells or blood cells. This approach will identify biomarkers for product characterization, patient safety and surrogate markers of response.
Mission Relevance & Outcomes: Ongoing critical path research activities provide the knowledge and tools for evaluating and supporting the development of safe and effective cell and gene therapy and tumor vaccine products for a variety of diseases including cancer.
Publications
Cancer Res 2008 Nov 15;68(22):9311-7
Human Adrenomedullin Up-regulates Interleukin-13 Receptor {alpha}2 Chain in Prostate Cancer In vitro and In vivo: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy.
Joshi BH, Leland P, Calvo A, Green JE, Puri RK
J Immunol 2008 Oct 1;181(7):4656-65
Novel Role of IL-13 in Fibrosis Induced by Nonalcoholic Steatohepatitis and Its Amelioration by IL-13R-Directed Cytotoxin in a Rat Model.
Shimamura T, Fujisawa T, Husain SR, Kioi M, Nakajima A, Puri RK
Genomics 2008 Sep;92(3):144-51
Anaplasma phagocytophilum-induced gene expression in both human neutrophils and HL-60 cells.
Lee HC, Kioi M, Han J, Puri RK, Goodman JL
Mol Ther 2008 Sep;16(9):1556-64
Interleukin-13 displaying retargeted oncolytic measles virus strains have significant activity against gliomas with improved specificity.
Allen C, Paraskevakou G, Iankov I, Giannini C, Schroeder M, Sarkaria J, Schroeder M, Puri RK, Russell SJ, Galanis E
Int J Cancer 2008 Sep 17;123(12):2915-2922
Potent in vitro and in vivo antitumor activity of interleukin-4-conjugated Pseudomonas exotoxin against human biliary tract carcinoma.
Ishige K, Shoda J, Kawamoto T, Matsuda S, Ueda T, Hyodo I, Ohkohchi N, Puri RK, Kawakami K
BMC Bioinformatics 2008 Aug 12;9 Suppl 9:S10
The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies.
Shi L, Jones WD, Jensen RV, Harris SC, Perkins RG, Goodsaid FM, Guo L, Croner LJ, Boysen C, Fang H, Qian F, Amur S, Bao W, Barbacioru CC, Bertholet V, Cao XM, Chu TM, Collins PJ, Fan XH, Frueh FW, Fuscoe JC, Guo X, Han J, Herman D, Hong H, Kawasaki ES, Li QZ, Luo Y, Ma Y, Mei N, Peterson RL, Puri RK, Shippy R, Su Z, Sun YA, Sun H, Thorn B, Turpaz Y, Wang C, Wang SJ, Warrington JA, Willey JC, Wu J, Xie Q, Zhang L, Zhang L, Zhong S, Wolfinger RD, Tong W
Neuro Oncol 2008 Jun;10(3):265-74
Identification of interleukin-13 receptor {alpha}2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma.
Joshi BH, Puri RA, Leland P, Varricchio F, Gupta G, Kocak M, Gilbertson RJ, Puri RK, U.S. Pediatric Brain Tumor Consortium
Mol Cancer Ther 2008 Jun;7(6):1579-1587
Targeting IL-13R{alpha}2-positive cancer with a novel recombinant immunotoxin composed of a single-chain antibody and mutated Pseudomonas exotoxin.
Kioi M, Seetharam S, Puri RK
BMC Genomics 2008 Jun 16;9:289
Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain.
Sharma A, Bhattacharya B, Puri RK, Maheshwari RK
BMC Cancer 2008 May 12;8:133
Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis.
Hubbard K, Catalano J, Puri RK, Gnatt A
Neurosurgery 2007 Nov;61(5):1031-8
Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase 1 study of final safety results.
Vogelbaum MA, Sampson JH, Kunwar S, Chang SM, Shaffrey M, Asher AL, Lang FF, Croteau D, Parker K, Grahn AY, Sherman JW, Husain SR, Puri RK
Biochem Biophys Res Commun 2007 May 18;356(4):1017-23
Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples.
Hsia CC, Chizhikov VE, Yang AX, Selvapandiyan A, Hewlett I, Duncan R, Puri RK, Nakhasi HL, Kaplan GG
J Clin Oncol 2007 Mar 1;25(7):837-44
Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the Cintredekin Besudotox Intraparenchymal Study Group.
Kunwar S, Prados MD, Chang SM, Berger MS, Lang FF, Piepmeier JM, Sampson JH, Ram Z, Gutin PH, Gibbons RD, Aldape KD, Croteau DJ, Sherman JW, Puri RK; Cintredekin Besudotox Intraparenchymal Study Group
AJR Am J Roentgenol 2007 Mar;188(3):703-9
Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin.
Sampson JH, Raghavan R, Provenzale JM, Croteau D, Reardon DA, Coleman RE, Rodriguez Ponce I, Pastan I, Puri RK, Pedain C
Mol Biotechnol 2006 Nov;34(3):303-15
Analysis of the quality of contact pin fabricated oligonucleotide microarrays.
Yang AX, Mejido J, Bhattacharya B, Petersen D, Han J, Kawasaki ES, Puri RK
FASEB J 2006 Nov;20(13):2378-80
N-linked glycosylation of IL-13R{alpha}2 is essential for optimal IL-13 inhibitory activity.
Kioi M, Seetharam S, Puri RK
Cancer 2006 Sep 15;107(6):1407-18
Interleukin-13 receptor alpha2 chain: a potential biomarker and molecular target for ovarian cancer therapy.
Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK
Vitam Horm 2006;74C:479-504
Role of Interleukin-13 in Cancer, Pulmonary Fibrosis, and Other T(H)2-Type Diseases.
Joshi BH, Hogaboam C, Dover P, Husain SR, Puri RK
Clin Cancer Res 2006 Aug 1;12(15):4678-86
Intratumoral Therapy with IL13-PE38 Results in Effective CTL-Mediated Suppression of IL-13R{alpha}2-Expressing Contralateral Tumors.
Kawakami K, Terabe M, Kioi M, Berzofsky JA, Puri RK
Technol Cancer Res Treat 2006 Jun;5(3):239-50
Convection-enhanced Delivery of Interleukin-13 Receptor-directed Cytotoxin for Malignant Glioma Therapy.
Kioi M, Husain SR, Croteau D, Kunwar S, Puri RK
Stem Cells Dev 2006 Jun;15(3):315-23
Comparisons between transcriptional regulation and RNA expression in human embryonic stem cell lines.
Player A, Wang Y, Bhattacharya B, Rao M, Puri RK, Kawasaki ES
Genomics 2006 Apr;87(4):552-9
Quality prediction of cell substrate using gene expression profiling.
Han J, Farnsworth RL, Tiwari JL, Tian J, Lee H, Ikonomi P, Byrnes AP, Goodman JL, Puri RK
Cancer Res 2006 Apr 15;66(8):4434-42
Characterization of a Novel Human Tumor Antigen Interleukin-13 Receptor {alpha}2 Chain.
Kawakami K, Terabe M, Kawakami M, Berzofsky JA, Puri RK
Neurosurg Focus 2006 Apr 15;20(4):e15
Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.
Kunwar S, Chang SM, Prados MD, Berger MS, Sampson JH, Croteau D, Sherman JW, Grahn AY, Shu VS, Dul JL, Husain SR, Joshi BH, Pedain C, Puri RK
Neurosurg Focus 2006 Apr 15;20(4):e11
The IL-4 and IL-13 pseudomonas exotoxins: new hope for brain tumor therapy.
Shimamura T, Husain SR, Puri RK
Nat Med 2006 Jan;12(1):99-106
IL-13 signaling through the IL-13alpha(2) receptor is involved in induction of TGF-beta(1) production and fibrosis.
Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A
BMC Dev Biol 2005 Oct 5;5:22
Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies.
Bhattacharya B, Cai J, Luo Y, Miura T, Mejido J, Brimble SN, Zeng X, Schulz TC, Rao MS, Puri RK
Int J Radiat Oncol Biol Phys 2005 Sep 1;63(1):230-7
Combined effects of radiation and interleukin-13 receptor-targeted cytotoxin on glioblastoma cell lines.
Kawakami K, Kawakami M, Liu Q, Puri RK
Leuk Res 2005 Sep;29(9):1009-18
A recombinant IL-4-Pseudomonas exotoxin inhibits protein synthesis and overcomes apoptosis resistance in human CLL B cells.
Kay NE, Bone ND, Lee YK, Jelinek DF, Leland P, Battle TE, Frank DA, Puri RK
Cancer Res 2005 Sep 15;65(18):8388-96
Expression and targeting of interleukin-4 receptor for primary and advanced ovarian cancer therapy.
Kioi M, Takahashi S, Kawakami M, Kawakami K, Kreitman RJ, Puri RK
Int J Cancer 2005 Aug 10;116(1):1-8
Adenoviral vector-mediated gene transfer of IL-13Ralpha2 chain followed by IL-13 cytotoxin treatment offers potent targeted therapy for cytotoxin-resistant cancers.
Saito M, Murata T, Watanabe K, Kawakami K, Suzuki M, Koji T, Puri RK, Kitazato K, Kobayashi N
Genomics 2005 Jun 9;86(2):252-8.
Novel multiple 5'-amino-modified primer for DNA microarrays.
Han J, Lee H, Nguyen NY, Beaucage SL, Puri RK.
BMC Bioinformatics 2005 Jul 15;6 Suppl 2:S11
Microarray scanner calibration curves: characteristics and implications.
Shi L, Tong W, Su Z, Han T, Han J, Puri RK, Fang H, Frueh FW, Goodsaid FM, Guo L, Branham WS, Chen JJ, Xu ZA, Harris SC, Hong H, Xie Q, Perkins RG, Fuscoe JC
BMC Bioinformatics 2005 Jul 15;6 Suppl 2:S12
Cross-platform comparability of microarray technology: intra-platform consistency and appropriate data analysis procedures are essential.
Shi L, Tong W, Fang H, Scherf U, Han J, Puri RK, Frueh FW, Goodsaid FM, Guo L, Su Z, Han T, Fuscoe JC, Xu ZA, Patterson TA, Hong H, Xie Q, Perkins RG, Chen JJ, Casciano DA
J Immunother 2005 Jul-Aug;28(4):376-81
Phase I trial of intravenous IL-4 pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor.
Garland L, Gitlitz B, Ebbinghaus S, Pan H, de Haan H, Puri RK, Von Hoff D, Figlin R
Stem Cells Dev 2005 Jun;14(3):270-84
Development of a focused microarray to assess human embryonic stem cell differentiation.
Yang AX, Mejido J, Luo Y, Zeng X, Schwartz C, Wu T, Thies RS, Bhattacharya B, Han J, Freed B, Rao M, Puri RK
Supplementary Material
J Immunother 2005 May-Jun;28(3):193-202
Evidence That IL-13Ralpha2 Chain in Human Glioma Cells Is Responsible for the Antitumor Activity Mediated by Receptor-Directed Cytotoxin Therapy.
Kawakami K, Kioi M, Liu Q, Kawakami M, Puri RK
Cancer 2005 May 15;103(10):2132-42
Expression and structure of interleukin 4 receptors in primary meningeal tumors.
Puri S, Joshi BH, Sarkar C, Mahapatra AK, Hussain E, Sinha S
BMC Genomics 2005 May 5;6(1):63
Three microarray platforms: an analysis of their concordance in profiling gene expression.
Petersen D, Chandramouli GV, Geoghegan J, Hilburn J, Paarlberg J, Kim CH, Munroe D, Gangi L, Han J, Puri R, Staudt L, Weinstein J, Barrett JC, Green J, Kawasaki ES
Curr Gene Ther 2005 Apr;5(2):213-23
Cancer gene therapy utilizing interleukin-13 receptor alpha2 chain.
Kawakami K
J Neurooncol 2005 Mar;72(1):35-46
Analysis of target genes induced by IL-13 cytotoxin in human glioblastoma cells.
Han J, Yang L, Puri RK
Protein Expr Purif 2005 Feb;39(2):189-98
Optimization of expression and purification of two biologically active chimeric fusion proteins that consist of human interleukin-13 and Pseudomonas exotoxin in Escherichia coli.
Joshi BH, Puri RK
J Neurosurg 2005 Feb;102(2):267-75
Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma.
Parney IF, Kunwar S, McDermott M, Berger M, Prados M, Cha S, Croteau D, Puri RK, Chang SM
J Neurosurg 2004 Dec;101(6):1004-11
Distribution kinetics of targeted cytotoxin in glioma by bolus or convection-enhanced delivery in a murine model.
Kawakami K, Kawakami M, Kioi M, Husain SR, Puri RK
Blood 2004 Dec 30; [Epub ahead of print]
Hodgkin's lymphoma therapy with interleukin-4 receptor-directed cytotoxin in an infiltrating animal model.
Kawakami M, Kawakami K, Kioi M, Leland P, Puri RK
Dev Biol 2004;116:53-9
Regulatory expectations during product development for tumour vaccines.
Kawakami K, Puri RK
Immunol Res 2004;30(3):339-49
Therapeutic targeting of IL-4- and IL-13-responsive cells in pulmonary fibrosis.
Jakubzick C, Kunkel SL, Puri RK, Hogaboam CM
Cancer 2004 Sep 1;101(5):1036-42
Analysis of interleukin-13 receptor alpha2 expression in human pediatric brain tumors.
Kawakami M, Kawakami K, Takahashi S, Abe M, Puri RK
Clin Cancer Res 2004 Sep 15;10(18):6231-8
Analysis of Antitumor Activity of an Interleukin-13 (IL-13) Receptor-Targeted Cytotoxin Composed of IL-13 Antagonist and Pseudomonas Exotoxin.
Kioi M, Kawakami K, Puri RK
Clin Cancer Res 2004 Aug 1;10(15):5264-70
Nitric oxide accelerates interleukin-13 cytotoxin-mediated regression in head and neck cancer animal model.
Kawakami K, Kawakami M, Puri RK
Ann Thorac Surg 2004 Aug;78(2):436-43
Interleukin-4 receptor cytotoxin as therapy for human malignant pleural mesothelioma xenografts.
Beseth BD, Cameron RB, Leland P, You L, Varricchio F, Kreitman RJ, Maki RA, Jablons DM, Husain SR, Puri RK
Am J Pathol 2004 Jun;164(6):1989-2001
Human pulmonary fibroblasts exhibit altered interleukin-4 and interleukin-13 receptor subunit expression in idiopathic interstitial pneumonia.
Jakubzick C, Choi ES, Carpenter KJ, Kunkel SL, Evanoff H, Martinez FJ, Flaherty KR, Toews GB, Colby TV, Travis WD, Joshi BH, Puri RK, Hogaboam CM
Stem Cells 2004 May;22(3):292-312
Properties of Pluripotent Human Embryonic Stem Cells BG01 and BG02.
Zeng X, Miura T, Luo Y, Bhattacharya B, Condie B, Chen J, Ginis I, Lyons I, Mejido J, Puri RK, Rao MS, Freed WJ
Cell Immunol 2004 May;229(1):41-51
Mechanism of action of interleukin-13 antagonist (IL-13E13K) in cells expressing various types of IL-4R.
Kioi M, Kawakami K, Puri RK