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  1. Biologics Research Projects

Development of Safe and Effective Tumor Vaccines and Gene Therapy Products

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

General Overview

Cancer is a very complex public health problem. According to American Cancer Society more than one million Americans are diagnosed with cancer each year and about half of these cancer patients die from this dreadful disease. Despite enormous efforts to find a cure, overall survival of cancer patients remains dismal and new therapeutic approaches are urgently needed. Recent advances in cancer immunotherapy has shown a remarkable potential to make cancer cure a reality.

Our laboratory is engaged in research in the areas of cancer vaccines, immunotherapy, cellular and gene therapy. We also investigate how advanced medical technologies such as genomics can contribute to the study and development of those products. Genomics is the study of the expression and function of thousands of different genes and microRNAs.

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

The FDA is reviewing numerous investigational cancer vaccines, immunotherapy and gene therapy products for investigational use. However, there are limited numbers of licensed products of this nature for clinical use. The main barriers to successful product development are a limited understanding of the biology of tumors, limited knowledge on unique targets on cancer and the lack of appropriate tests to determine unique characteristics, purity and potency of potential products. There is also a lack of reliable animal models that scientists can utilize to evaluate and predict the safety and efficacy of these promising products and methods to monitor meaningful tumor responses in patients. In addition, there is a severe paucity of biomarkers that can help in early diagnosis, predict prognosis and response to cancer therapy.

Our group is currently addressing these issues by developing in vitro and in vivo research programs to increase our understanding of 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. We will also be able to share this new knowledge by organizing workshops and providing education and outreach to numerous stakeholders. Altogether, our work will bring recognition and trust to FDA and its regulatory mission.

Scientific Overview

The overall aims of our research projects are to develop a better comprehension of tumor characteristics through identification and characterization of potential tumor-associated cell surface proteins. These surface proteins will aid in establishing the identity and potency of tumor vaccines (e.g., receptors for IL-13 and IL-4), and potentially lead to methods that link product characteristics with clinical outcome.

In addition, we are studying the mechanism of regulation of over-expressed receptors and tumor antigens and their involvement in other cellular or molecular pathways, such as ontogenesis and signal transduction. This work includes in vitro studies and in vivo animal models of human cancer to elucidate mechanisms of tumor invasion and metastasis that may facilitate identification of additional novel targets or biomarkers for detecting cancer and evaluating therapeutic responses. Furthermore, this work may benefit in the development of new release tests based on the discovery of new biomarkers for identity, potency, and stability for different types of cancer vaccines.

We have established various animal models including orthotopic models of human cancer that are used to evaluate the safety and efficacy of cancer vaccines, cell and gene therapy products. In addition, we are using genomics technology to identify characteristics of cellular cancer vaccines, stem cells and cell substrates used to manufacture cellular and gene therapy products. This technology identifies unique sets of genes that are highly differentially expressed, thus providing a molecular signature of tumors, stem cells, cancer stem cells, or blood cells. This high throughput approach will helps us identifying biomarkers for product characterization, patient safety, and surrogate markers of tumor response.

Our research studies are being conducted under two main projects:

Project 1. Cancer Vaccines and Immunotherapy

The following aims are studied under this project:

Aim 1. Identification, characterization, signaling through novel tumor antigens/receptors and targeting of these receptors for cancer therapy. These studies will potentially help in establishing the identity, purity and potency of cancer vaccines and cancer immunotherapy products. In addition, animal models of human cancer will help assessing safety and efficacy of tumor-targeted agents, cancer vaccines, and immunotherapy products as monotherapy or in combination therapy.

Aim 2. Development of safe and effective cancer vaccines including DNA plasmid or recombinant vaccinia viral vectors expressing human IL-13R2. In addition, molecular characterization of human immature and mature dendritic cells and identification of biomarker of antigen presentation when
pulsed with antigens/peptides as cancer vaccine.

Aim 3. Adoptive Immunotherapy of cancer using CAR-T or engineered TCR cells targeting IL-13 receptor alpha 2

Project 2. Application of Genomics technology: Characterization of Cell and Gene therapy and cancer vaccines products

The following aims are studied under this project:

Aim 1. Characterization of cell banks, cancer vaccines and stem cells by genomics technology to identify markers of purity, identity, potency and targets for therapy

Aim 2. Analysis of IL-4 receptors and IL-13 receptors as potential biomarkers of disease, prognosis and monitoring of tumor response by analyzing publically available The Cancer Genome Atlas (TCGA) database.


BMC Genomics 2017 Aug 11;18(1):605
MicroRNA expression in bone marrow-derived human multipotent Stromal cells.
Bellayr IH, Kumar A, Puri RK

Tissue Eng Part A 2017 Jun;23(11-12):471-3
Current status and challenges of three-dimensional modeling and printing of tissues and organs.
Husain SR, Ohya Y, Puri RK

BMC Infect Dis 2017 Apr 26;17(1):309
Differential host gene responses from infection with neurovirulent and partially-neurovirulent strains of Venezuelan equine encephalitis virus.
Gupta P, Sharma A, Han J, Yang A, Bhomia M, Knollmann-Ritschel B, Puri RK, Maheshwari RK

Stem Cells Dev 2016 Jun 1;25(11):861-73
Identification of predictive gene markers for multipotent stromal cell proliferation.
Bellayr IH, Marklein RA, Lo Surdo JL, Bauer SR, Puri RK

Stem Cells 2016 Apr;34(4):935-47
High content imaging of early morphological signatures predicts long term mineralization capacity of human mesenchymal stem cells upon osteogenic induction.
Marklein RA, Lo Surdo JL, Bellayr IH, Godil SA, Puri RK, Bauer SR

Blood Cells Mol Dis 2015 Dec;55(4):373-81
Gene expression profile of circulating CD34(+) cells and granulocytes in chronic myeloid leukemia.
Cokic VP, Mojsilovic S, Jaukovic A, Kraguljac-Kurtovic N, Mojsilovic S, Sefer D, Mitrovic Ajtic O, Milosevic V, Bogdanovic A, Dikic D, Milenkovic P, Puri RK

Cancer Gene Ther 2015 Dec;22(12):554-63
Gene therapy for cancer: regulatory considerations for approval.
Husain SR, Han J, Au P, Shannon K, Puri RK

Discov Med 2015 Nov;20(111):273-84
Identification, characterization, and targeting of IL-4 receptor by IL-4-Pseudomonas exotoxin in mouse models of anaplastic thyroid cancer.
Joshi BH, Suzuki A, Fujisawa T, Leland P, Varrichio F, Lababidi S, Lloyd R, Kasperbauer J, Puri RK

Cytokine 2015 Sep;75(1):79-88
Targeting of IL-4 and IL-13 receptors for cancer therapy.
Suzuki A, Leland P, Joshi BH, Puri RK

Mediators Inflamm 2015;2015:453020
Proinflammatory cytokine IL-6 and JAK-STAT signaling pathway in myeloproliferative neoplasms.
Cokic VP, Mitrovic-Ajtic O, Beleslin-Cokic BB, Markovic D, Buac M, Diklic M, Kraguljac-Kurtovic N, Damjanovic S, Milenkovic P, Gotic M, Raj PK

PLoS One 2015 Aug 14;10(8):e0135463
Microarray and proteomic analyses of myeloproliferative neoplasms with a highlight on the mTOR signaling pathway.
Cokic VP, Mossuz P, Han J, Socoro N, Beleslin-Cokic BB, Mitrovic O, Suboticki T, Diklic M, Lekovic D, Gotic M, Puri RK, Noguchi CT, Schechter AN

Cancer Med 2015 Jul;4(7):1060-8
Phase I trial of systemic intravenous infusion of interleukin-13-Pseudomonas exotoxin in patients with metastatic adrenocortical carcinoma.
Liu-Chittenden Y, Jain M, Kumar P, Patel D, Aufforth R, Neychev V, Sadowski S, Gara SK, Joshi BH, Cottle-Delisle C, Merkel R, Yang L, Miettinen M, Puri RK, Kebebew E

Urol Oncol 2015 Mar;33(3):133-6
Regulation of biologic oncology products in the FDA's Center for Biologics Evaluation and Research.
Bross PF, Fan C, George B, Shannon K, Joshi BH, Puri RK

Cancer Med 2014 Dec;3(6):1615-28
Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.
Joshi BH, Leland P, Lababidi S, Varrichio F, Puri RK

Gut 2014 Nov;63(11):1728-36
IL-13Ralpha2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis.
Fuss IJ, Joshi B, Yang Z, Degheidy H, Fichtner-Feigl S, de Souza H, Rieder F, Scaldaferri F, Schirbel A, Scarpa M, West G, Yi C, Xu L, Leland P, Yao M, Mannon P, Puri RK, Fiocchi C, Strober W

J Nucl Med 2014 Aug;55(8):1323-9
Analysis of biodistribution of intracranially infused radiolabeled interleukin-13 receptor-targeted immunotoxin IL-13PE by SPECT/CT in an orthotopic mouse model of human glioma.
Suzuki A, Leland P, Kobayashi H, Choyke PL, Jagoda EM, Inoue T, Joshi BH, Puri RK

Stem Cell Res Ther 2014 Apr 28;5(2):59
Gene markers of cellular aging in human multipotent stromal cells in culture.
Bellayr IH, Catalano JG, Lababidi S, Yang AX, Lo Surdo JL, Bauer SR, Puri RK

BMC Cancer 2014 Mar 11;14:173
Identification and characterization of cancer stem cells in human head and neck squamous cell carcinoma.
Han J, Fujisawa T, Husain SR, Puri RK

Cell Stem Cell 2014 Feb 6;14(2):141-5
MSC-based product characterization for clinical trials: an FDA perspective.
Mendicino M, Bailey AM, Wonnacott K, Puri RK, Bauer SR

PLoS One 2014 Jan 27;9(1):e86306
Molecular characterization of antigen-Peptide pulsed dendritic cells: immature dendritic cells develop a distinct molecular profile when pulsed with antigen Peptide.
Yang AX, Chong N, Jiang Y, Catalano J, Puri RK, Khleif SN

J Immunol 2013 Nov 15;191(10):5220-9
IL-13 Immunotoxin Accelerates Resolution of Lung Pathological Changes Triggered by Silica Particles in Mice.
Ferreira TP, de Arantes AC, do Nascimento CV, Olsen PC, Trentin PG, Rocco PR, Hogaboam CM, Puri RK, Martins MA, Silva PM

Diabetes 2013 Nov;62(11):3785-96
Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT-cell stimulation: role of suppressive macrophages.
Ghazarian L, Diana J, Beaudoin L, Larsson PG, Puri RK, van Rooijen N, Flodstrom-Tullberg M, Lehuen A

Oncogene 2013 Aug 15;32(33):3857-66
The tumor suppressor Caliban regulates DNA damage-induced apoptosis through p53-dependent and -independent activity.
Wang Y, Wang Z, Joshi BH, Puri RK, Stultz B, Yuan Q, Bai Y, Zhou P, Yuan Z, Hursh DA, Bi X

J Immunother Cancer 2013 May 29;1:5
Regulation of immunotherapeutic products for cancer and FDA's role in product development and clinical evaluation.
Vatsan RS, Bross PF, Liu K, Theoret M, De Claro AR, Lu J, Helms W, Niland B, Husain SR, Puri RK

J Interferon Cytokine Res 2013 Apr;33(4):154-61
Immunomodulatory effects of interferons in malignancies.
Bekisz J, Sato Y, Johnson C, Husain SR, Puri RK, Zoon KC

Mol Ther 2013 Feb;21(2):476-84
Quality controls in cellular immunotherapies: rapid assessment of clinical grade dendritic cells by gene expression profiling.
Castiello L, Sabatino M, Zhao Y, Tumaini B, Ren J, Ping J, Wang E, Wood LV, Marincola FM, Puri RK, Stroncek DF

J Transl Med 2013 Feb 19;11:45
Targeting of interleukin-13 receptor alpha2 for treatment of head and neck squamous cell carcinoma induced by conditional deletion of TGF-beta and PTEN signaling.
Hall B, Nakashima H, Sun ZJ, Sato Y, Bian Y, Husain SR, Puri RK, Kulkarni AB

BMC Genomics 2013 Feb 20;14:116
Globin gene expression in correlation with G protein-related genes during erythroid differentiation.
Cokic VP, Smith RD, Biancotto A, Noguchi CT, Puri RK, Schechter AN

Exp Biol Med 2012 Dec 1;237(12):1413-23
Differentially expressed genes and pathways induced by organophosphates in human neuroblastoma cells.
Li T, Zhao H, Hung GC, Han J, Tsai S, Li B, Zhang J, Puri RK, Lo SC

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

Biotechnol Prog 2012 Sep;28(5):1126-37
Genomic analysis of a hybridoma batch cell culture metabolic status in a standard laboratory 5 L bioreactor.
Kondragunta B, Han J, Joshi BH, Brorson KA, Puri RK, Uplekar S, Moreira AR, Rao G

Biotechnol Prog 2012 Sep;28(5):1138-51
Bioreactor environment sensitive sentinel genes as novel metrics for cell culture scale-down comparability.
Kondragunta B, Joshi BH, Han J, Brorson KA, Puri RK, Moreira AR, Rao G

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

J Transl Med 2012 Jun 7;10:116
JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny.
Cokic VP, Bhattacharya B, Beleslin-Cokic BB, Noguchi CT, Puri RK, Schechter AN

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 alpha2 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):2915-22
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