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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Development of Safe and Effective Tumor Vaccines and Gene Therapy Products

Principal Investigator: Raj K. Puri, MD, PhD
Office / Division / Lab: OCTGT / DCGT / TVBB


General Overview

More than 1.3 million Americans are diagnosed with cancer each year and approximately half of them die. Despite enormous efforts to find a cure, overall survival of cancer patients has not increased and new therapeutic approaches are needed.

Our laboratory does research in the areas of tumor vaccines, cancer immunotherapy, cellular therapy, and gene therapy. We also study how advanced medical technologies such as genomics and multiplex cellular identification can contribute to the study and development of those products. Genomics is the study of the simultaneous state of activity of thousands of different genes; multiplex cellular identification is a technique for rapidly and automatically identifying the different types of cells that occur in a population of thousands or millions of cells.

The issues raised by cancer vaccines and cellular and gene therapies are extraordinarily complex, multifaceted, and subject to rapid change as technology progresses. These therapies are rapidly evolving and continue to pose regulatory challenges to FDA. Our laboratory is addressing this problem by evaluating these complex, emerging medical products and facilitating development of safe and effective therapies based on those products.

The FDA is now reviewing many investigational cancer gene therapies and tumor vaccine products for investigational use. However, there are as yet no such licensed products in clinical use. The main barriers to successful product development are a limited understanding of the biology of tumors, and the lack of appropriate tests for determining the unique characteristics and potency of products. There is also a lack of animal models that scientists can use to evaluate the safety and efficacy of these promising products and determine how to monitor tumor responses in patients.

Our group is currently addressing these issues by developing in vitro and in vivo research programs to help us understand how these products work in the body. Such knowledge will help FDA regulatory scientists conduct informed scientific evaluation of products, develop effective policies, and write documents that provide valuable guidance for industry in these areas of product development. We will also be able to share this new knowledge by organizing workshops and providing education and outreach to numerous stakeholders.


Scientific Overview

In order to fulfill the mission and commitments to characterize and help develop safe and effective tumor vaccines, and cellular and gene therapy products, our laboratory is pursuing the following projects:

1. Identifying and characterizing tumor-associated cell surface proteins (antigens or receptors) to establish identity and potency of tumor vaccines and targeting of receptors for cancer therapy

2. Developing animal models of human cancer to assess safety and efficacy of tumor-targeted agents, tumor vaccines, immunotherapy and gene therapy products as monotherapy or combination therapy

3. Characterizing master cell banks, tumor vaccines and stem cells by genomics technology to identify biomarkers of purity, identity, potency and targets for therapy and monitoring

4. Identifying and characterizing cancer stem cells in human cancers by molecular profiling of human embryonic stem cells and targeting of cancer stem cells for cancer therapy

The goals of our research program are to understand tumor characteristics, identify and characterize potential tumor-associated cell surface proteins that can be used to establish identity and potency of tumor vaccines (e.g., receptors for IL-13 and IL-4), and find ways to link product characteristics with clinical outcome.

In addition, we are studying the mechanism of regulation of over-expressed receptors and tumor antigens in vitro and in vivo and the involvement of other cellular or molecular targets in the oncogenesis and signal transduction pathways. This work includes in vitro studies as well as animal models of human cancer to elucidate mechanisms of tumor invasion and metastasis,and to identify additional novel targets or biomarkers for detecting cancer and monitoring therapeutic responses. This work might also help us to develop new release tests based on biomarkers for identity, potency, and stability of different types of cancer vaccines.

We have also established various animal models of human cancer that may be used to evaluate safety and efficacy of tumor vaccines, gene therapy and cancer targeted products. In addition, we are using genomics technology to identify characteristics of cellular tumor vaccines, stem cells and cell substrates used to manufacture cellular and gene therapy products. This technology identifies unique set of genes that are highly over expressed, thus providing a molecular signature of tumors, stem cells, cancer stem cells, or blood cells. This novel approach is helping us to identify biomarkers for product characterization, patient safety, and surrogate markers of tumor response.

The technical expertise acquired through research projects allows Dr. Puri and his laboratory personnel to actively participate and contribute in the regulatory review and development of policy and guidance documents. Such expertise also enables us to assist FDA regulatory scientists to perform informed scientific evaluation of original submissions or amendments of investigational new drug applications, master files, biologic license applications, and to organize workshops and provide education and outreach to numerous stakeholders.


Publications

Cancer 2012 Nov 15;118(22):5698-708
Interleukin-13 receptor alpha2 is a novel therapeutic target for human adrenocortical carcinoma.
Jain M, Zhang L, He M, Patterson EE, Nilubol N, Fojo AT, Joshi B, Puri R, Kebebew E

Int J Cancer 2012 Jul 15;131(2):344-56
IL-13 regulates cancer invasion and metastasis through IL-13Ralpha2 via ERK/AP-1 pathway in mouse model of human ovarian cancer.
Fujisawa T, Joshi BH, Puri RK

Cancer Immunol Immunother 2012 Jul;61(7):1081-92
Potent antitumor effects of combination therapy with IFNs and monocytes in mouse models of established human ovarian and melanoma tumors.
Nakashima H, Miyake K, Clark CR, Bekisz J, Finbloom J, Husain SR, Baron S, Puri RK, Zoon KC

PLoS One 2012;7(4):e34437
Cysteamine suppresses invasion, metastasis and prolongs survival by inhibiting matrix metalloproteinases in a mouse model of human pancreatic cancer.
Fujisawa T, Rubin B, Suzuki A, Patel PS, Gahl WA, Joshi BH, Puri RK

Immunotherapy 2012 Apr;4(4):443-51
IL-13 receptor-directed cancer vaccines and immunotherapy.
Nakashima H, Husain SR, Puri RK

Hum Gene Ther Methods 2012 Apr;23(2):137-47
Specific Targeting of Human Interleukin (IL)-13 Receptor alpha2-Positive Cells with Lentiviral Vectors Displaying IL-13.
Ou W, Marino MP, Suzuki A, Joshi B, Husain SR, Maisner A, Galanis E, Puri RK, Reiser J

Mol Cancer Ther 2012 Jan;11(1):235-43
Targeting interleukin-4 receptor alpha with hybrid peptide for effective cancer therapy.
Yang L, Horibe T, Kohno M, Haramoto M, Ohara K, Puri RK, Kawakami K

J Immunol 2011 Nov 15;187(10):4935-46
A novel combination immunotherapy for cancer by IL-13Ralpha2-targeted DNA vaccine and immunotoxin in murine tumor models.
Nakashima H, Terabe M, Berzofsky JA, Husain SR, Puri RK

Oral Oncol 2011 Sep;47(9):810-7
USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics.
Russell SM, Lechner MG, Gong L, Megiel C, Liebertz DJ, Masood R, Correa AJ, Han J, Puri RK, Sinha UK, Epstein AL

J Transl Med 2011 Apr 8;9:37
Histone modification enhances the effectiveness of IL-13 receptor targeted immunotoxin in murine models of human pancreatic cancer.
Fujisawa T, Joshi BH, Puri RK

Int J Cancer 2011 Mar 1;128(5):1221-31
Targeting IL-13Ralpha2 in human pancreatic ductal adenocarcinoma with combination therapy of IL-13-PE and gemcitabine.
Fujisawa T, Nakashima H, Nakajima A, Joshi BH, Puri RK

J Transl Med 2010 Nov 10;8:116
Interleukin-13 receptor α2 DNA prime boost vaccine induces tumor immunity in murine tumor models.
Nakashima H, Fujisawa T, Husain SR, Puri RK

Nat Biotechnol 2010 Aug;28(8):827-38
The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models.
MAQC Consortium, Shi L, Campbell G, Jones WD, Campagne F, Wen Z, Walker SJ, Su Z, Chu TM, Goodsaid FM, Pusztai L, Shaughnessy JD Jr, Oberthuer A, Thomas RS, Paules RS, Fielden M, Barlogie B, Chen W, Du P, Fischer M, Furlanello C, Gallas BD, Ge X, Megherbi DB, Symmans WF, Wang MD, Zhang J, Bitter H, Brors B, Bushel PR, Bylesjo M, Chen M, Cheng J, Cheng J, Chou J, Davison TS, Delorenzi M, Deng Y, Devanarayan V, Dix DJ, Dopazo J, Dorff KC, Elloumi F, Fan J, Fan S, Fan X, Fang H, Gonzaludo N, Hess KR, Hong H, Huan J, Irizarry RA, Judson R, Juraeva D, Lababidi S, Lambert CG, Li L, Li Y, Li Z, Lin SM, Liu G, Lobenhofer EK, Luo J, Luo W, McCall MN, Nikolsky Y, Pennello GA, Perkins RG, Philip R, Popovici V, Price ND, Qian F, Scherer A, Shi T, Shi W, Sung J, Thierry-Mieg D, Thierry-Mieg J, Thodima V, Trygg J, Vishnuvajjala L, Wang SJ, Wu J, Wu Y, Xie Q, Yousef WA, Zhang L, Zhang X, Zhong S, Zhou Y, Zhu S, Arasappan D, Bao W, Lucas AB, Berthold F, Brennan RJ, Buness A, Catalano JG, Chang C, Chen R, Cheng Y, Cui J, Czika W, Demichelis F, Deng X, Dosymbekov D, Eils R, Feng Y, Fostel J, Fulmer-Smentek S, Fuscoe JC, Gatto L, Ge W, Goldstein DR, Guo L, Halbert DN, Han J, Harris SC, Hatzis C, Herman D, Huang J, Jensen RV, Jiang R, Johnson CD, Jurman G, Kahlert Y, Khuder SA, Kohl M, Li J, Li L, Li M, Li QZ, Li S, Li Z, Liu J, Liu Y, Liu Z, Meng L, Madera M, Martinez-Murillo F, Medina I, Meehan J, Miclaus K, Moffitt RA, Montaner D, Mukherjee P, Mulligan GJ, Neville P, Nikolskaya T, Ning B, Page GP, Parker J, Parry RM, Peng X, Peterson RL, Phan JH, Quanz B, Ren Y, Riccadonna S, Roter AH, Samuelson FW, Schumacher MM, Shambaugh JD, Shi Q, Shippy R, Si S, Smalter A, Sotiriou C, Soukup M, Staedtler F, Steiner G, Stokes TH, Sun Q, Tan PY, Tang R, Tezak Z, Thorn B, Tsyganova M, Turpaz Y, Vega SC, Visintainer R, von Frese J, Wang C, Wang E, Wang J, Wang W, Westermann F, Willey JC, Woods M, Wu S, Xiao N, Xu J, Xu L, Yang L, Zeng X, Zhang J, Zhang L, Zhang M, Zhao C, Puri RK, Scherf U, Tong W, Wolfinger RD

Neuro Oncol 2010 Aug;12(8):871-81
Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma.
Kunwar S, Chang S, Westphal M, Vogelbaum M, Sampson J, Barnett G, Shaffrey M, Ram Z, Piepmeier J, Prados M, Croteau D, Pedain C, Leland P, Husain SR, Joshi BH, Puri RK, PRECISE Study Group

J Neurosurg 2010 Aug;113(2):301-9
Poor drug distribution as a possible explanation for the results of the PRECISE trial.
Sampson JH, Archer G, Pedain C, Wembacher-Schröder E, Westphal M, Kunwar S, Vogelbaum MA, Coan A, Herndon JE, Raghavan R, Brady ML, Reardon DA, Friedman AH, Friedman HS, Rodríguez-Ponce MI, Chang SM, Mittermeyer S, Croteau D, Puri RK, PRECISE Trial Investigators

Nat Rev Drug Discov 2010 Jun;9(6):435-45
Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact.
Goodsaid FM, Amur S, Aubrecht J, Burczynski ME, Carl K, Catalano J, Charlab R, Close S, Cornu-Artis C, Essioux L, Fornace AJ Jr, Hinman L, Hong H, Hunt I, Jacobson-Kram D, Jawaid A, Laurie D, Lesko L, Li HH, Lindpaintner K, Mayne J, Morrow P, Papaluca-Amati M, Robison TW, Roth J, Schuppe-Koistinen I, Shi L, Spleiss O, Tong W, Truter SL, Vonderscher J, Westelinck A, Zhang L, Zineh I

J Transl Med 2010 Mar 29;8:31
Cell and gene therapies: moving from research to clinic.
Stroncek DF, Puri RK

Clin Cancer Res 2010 Jan 15;16(2):577-86
Interleukin 13 Mediates Signal Transduction through Interleukin 13 Receptor {alpha}2 in Pancreatic Ductal Adenocarcinoma: Role of IL-13 Pseudomonas Exotoxin in Pancreatic Cancer Therapy.
Shimamura T, Fujisawa T, Husain SR, Joshi B, Puri RK

PLoS One 2010 Jan 15;5(1):e8721
Therapeutic efficacy of Cintredekin Besudotox (IL13-PE38QQR) in murine lung fibrosis is unaffected by immunity to Pseudomonas aeruginosa exotoxin A.
Rosada RS, Moreira AP, Frantz FG, Puri RK, Rahman A, Standiford TJ, Zárate-Bladés CR, Silva CL, Hogaboam CM

Cancer Res 2009 Nov 15;69(22):8678-85
A Novel Role of Interleukin-13 Receptor {alpha}2 in Pancreatic Cancer Invasion and Metastasis.
Fujisawa T, Joshi B, Nakajima A, Puri RK

J Clin Endocrinol Metab 2009 Aug;94(8):2952-7
Overexpression of interleukin-13 receptor-alpha2 in neuroendocrine malignant pheochromocytoma: a novel target for receptor directed anti-cancer therapy.
Lai EW, Joshi BH, Martiniova L, Dogra R, Fujisawa T, Leland P, de Krijger RR, Lubensky IA, Elkahloun AG, Morris JC, Puri RK, Pacak K

Curr Mol Med 2009 Aug;9(6):665-6
Tumor immunology.
Joshi BH, Puri RK

Curr Mol Med 2009 Aug;9(6):732-9
A review of studies on targeting interleukin 4 receptor for central nervous system malignancy.
Puri S, Puri S, Mahapatra AK, Hussain E, Sarkar C, Sinha S, Joshi BH

Head Neck Oncol 2009 Jul 14;1(1):27
Identification of potential therapeutic targets in human head & neck squamous cell carcinoma.
Han J, Kioi M, Chu WS, Kasperbauer JL, Strome SE, Puri RK

Curr Stem Cell Res Ther 2009 May;4(2):98-106
A Review of Gene Expression Profiling of Human Embryonic Stem Cell Lines and their Differentiated Progeny.
Bhattacharya B, Puri S, Puri RK

Int J Cancer 2009 Mar 15;124(6):1440-8
IL-13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma.
Kioi M, Shimamura T, Nakashima H, Hirota M, Tohnai I, Husain SR, Puri RK

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):1579-87
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

Cancer Res 2007 Oct 15;67(20):9903-12
Interleukin-4 cytotoxin therapy synergizes with gemcitabine in a mouse model of pancreatic ductal adenocarcinoma.
Shimamura T, Royal RE, Kioi M, Nakajima A, 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

Neurosurgery 2007 Feb;60(2 Suppl 1):89-99
Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.
Sampson JH, Brady ML, Petry NA, Croteau D, Friedman AH, Friedman HS, Wong T, Bigner DD, Pastan I, Puri RK, Pedain C

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

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

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

Nat Biotechnol 2006 Sep 8;24(9):1151-1161
The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.
Shi L, Reid LH, Jones WD, Shippy R, Warrington JA, Baker SC, Collins PJ, de Longueville F, Kawasaki ES, Lee KY, Luo Y, Sun YA, Willey JC, Setterquist RA, Fischer GM, Tong W, Dragan YP, Dix DJ, Frueh FW, Goodsaid FM, Herman D, Jensen RV, Johnson CD, Lobenhofer EK, Puri RK, Scherf U, Thierry-Mieg J, Wang C, Wilson M, Wolber PK, Zhang L, Amur S, Bao W, Barbacioru CC, Lucas AB, Bertholet V, Boysen C, Bromley B, Brown D, Brunner A, Canales R, Cao XM, Cebula TA, Chen JJ, Cheng J, Chu TM, Chudin E, Corson J, Corton JC, Croner LJ, Davies C, Davison TS, Delenstarr G, Deng X, Dorris D, Eklund AC, Fan XH, Fang H, Fulmer-Smentek S, Fuscoe JC, Gallagher K, Ge W, Guo L, Guo X, Hager J, Haje PK, Han J, Han T, Harbottle HC, Harris SC, Hatchwell E, Hauser CA, Hester S, Hong H, Hurban P, Jackson SA, Ji H, Knight CR, Kuo WP, Leclerc JE, Levy S, Li QZ, Liu C, Liu Y, Lombardi MJ, Ma Y, Magnuson SR, Maqsodi B, McDaniel T, Mei N, Myklebost O, Ning B, Novoradovskaya N, Orr MS, Osborn TW, Papallo A, Patterson TA, Perkins RG, Peters EH, Peterson R, Philips KL, Pine PS, Pusztai L, Qian F, Ren H, Rosen M, Rosenzweig BA, Samaha RR, Schena M, Schroth GP, Shchegrova S, Smith DD, Staedtler F, Su Z, Sun H, Szallasi Z, Tezak Z, Thierry-Mieg D, Thompson KL, Tikhonova I, Turpaz Y, Vallanat B, Van C, Walker SJ, Wang SJ, Wang Y, Wolfinger R, Wong A, Wu J, Xiao C, Xie Q, Xu J, Yang W, Zhang L, Zhong S, Zong Y, Slikker W Jr

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

Blood 2005 May 1;105(9):3707-13
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

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

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

Blood 2004 Apr 15;103(8):2956-64
Gene Expression in Human Embryonic Stem Cell Lines: Unique Molecular Signature.
Bhattacharya B, Miura T, Brandenberg R, Mejido J, Luo Y, Yang AX, Joshi BH, Irene G, Thies RS, Amit M, Lyons I, Condie BG, Iskovitz-Eldor J, Rao MS, Puri RK

 

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