Specialized Resource B- Gene Transfer and Cell Engineering (SR-B). SR-B of ICMIC-3 will support preclinical and clinical gene transfer studies in RP1. It also provides support for engineering tumor cell lines for studies by RP2 and RP4. These projects are highly dependent on achieving efficient gene transfer in either primary T lymphocytes, packaging cell lines or tumor cell lines. In research and pre-clinical studies, the SR-B assists Investigators in the;1. Construction of recombinant oncoretroviral and lentiviral vectors 2. Transfection or transduction of vector in packaging cells and selection of producer cell lines 3. Characterization of vector transmission and stability 4. Expansion of packaging cell clones and identification of the best clone for the intended target cells 5. Titration of cell-free retroviral stocks 6. Detection of replication-competent retrovirus in viral stocks and transduced target cells 7. Detection of oncoretroviral and lentiviral vector integration sites by LM-PCR 8. Optimization of tumor cell lines and T lymphocyte transduction with retroviral vectors 9. Optimization of lymphocyte expansion ex vivo with Dynabeads? ClinExvivoCD3/CD28. In the clinical phase, the SR-B will carry out and/or coordinate the: 1. Generation of high-titer producer cell clones, master cell banks (MCB) and retroviral stocks for clinical studies 2. Production of clinical viral stocks 3. Expansion and transduction of patient cells in semi-closed systems in collaboration with the investigators of the clinical trial 4. Detection of RCR and other biosafety testing in cultured packaging cell clones (MCB), viral stocks and clinical specimens 5. Characterization of the expression of the transgene (imaging reporters or PSMA-CAR) by either RT-PCR or flow cytometry analysis in transduced patient cells 6. Determination of the vector copy number by Real time PCR in the peripheral blood, bone marrow samples and available tissues of the patients at different time points after infusion of the genetically modified T cells.

Public Health Relevance

This Specialized Resource will provide services and expertise in gene transfer, molecular analysis and cellular processes to Research Projects 1, 2 and 4. Through SR-B, the centralized generation of high-quality producer cell lines, of viral stocks and the development of procedures to efficiently engineer tumor cell lines and transduce patients T cells will permit standardization of procedures and facilitate the exchange of information, reagents and expertise between all the projects. It will also be cost effective.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA086438-13
Application #
8567123
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
13
Fiscal Year
2013
Total Cost
$205,658
Indirect Cost
$93,076
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Graham, Nicholas A; Minasyan, Aspram; Lomova, Anastasia et al. (2017) Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Mol Syst Biol 13:914
Serganova, Inna; Moroz, Ekaterina; Cohen, Ivan et al. (2017) Enhancement of PSMA-Directed CAR Adoptive Immunotherapy by PD-1/PD-L1 Blockade. Mol Ther Oncolytics 4:41-54
Pankov, Dmitry; Sjöström, Ludvig; Kalidindi, Teja et al. (2017) In vivo immuno-targeting of an extracellular epitope of membrane bound preferentially expressed antigen in melanoma (PRAME). Oncotarget 8:65917-65931
Kim, Kwanghee; Zhang, Hanwen; La Rosa, Stephen et al. (2017) Bombesin Antagonist-Based Radiotherapy of Prostate Cancer Combined with WST-11 Vascular Targeted Photodynamic Therapy. Clin Cancer Res 23:3343-3351
Lu, Shaohua; Tan, Kay See; Kadota, Kyuichi et al. (2017) Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma. J Thorac Oncol 12:223-234
Lee, Jason T; Zhang, Hanwen; Moroz, Maxim A et al. (2017) Comparative Analysis of Human Nucleoside Kinase-Based Reporter Systems for PET Imaging. Mol Imaging Biol 19:100-108
Kadota, Kyuichi; Sima, Camelia S; Arcila, Maria E et al. (2016) KRAS Mutation Is a Significant Prognostic Factor in Early-stage Lung Adenocarcinoma. Am J Surg Pathol 40:1579-1590
Adusumilli, Prasad S (2016) Spread through alveolar spaces: An aerogenous invasion in pulmonary adenocarcinomas. J Thorac Cardiovasc Surg 152:73-4
Taldone, Tony; Zatorska, Danuta; Ochiana, Stefan O et al. (2016) Radiosynthesis of the iodine-124 labeled Hsp90 inhibitor PU-H71. J Labelled Comp Radiopharm 59:129-32
Yeh, Yi-Chen; Kadota, Kyuichi; Nitadori, Jun-ichi et al. (2016) International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. Eur J Cardiothorac Surg 49:e9-e15

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