Abstract

Research Project 1 (RP1) builds on the progress and success of Projects 1 and 2 in ICMIC-2. Our hypothesis is that both constitutive and PSMA-activated reporter gene imaging of PSMA directed T cell targeting, distribution and persistence can be performed concurrently in patients with castrate resistant prostate cancer. The central theme of this proposal is consistent with our ICMIC:

Public Health Relevance

Project 1 involves a phase 1 clinical study to test whether genetically altered, PSMA directed, T cells can be monitored by non-invasive Positron Emission Tomography (PET) imaging, and whether the imaging results can provide an early indication of treatment response (or failure) in patients with castrate resistant prostate cancer. In parallel, preclinical imaging studies will evaluate the effect of an abnormal tumor microenvironment and the effect of tumor PSMA expression levels on: 1) PSMA-directed T cell targeting, activation and persistence, and on 2) the efficacy of tumor-modulated, PSMA-directed T cell therapy. Importantly, these imaging studies could be readily translated to clinic and serve as a model to study other cancers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA086438-13
Application #
8567119
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
$236,851
Indirect Cost
$107,193

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

McDevitt, Michael R; Thorek, Daniel L J; Hashimoto, Takeshi et al. (2018) Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer. Nat Commun 9:1629
Dunphy, Mark P S; Harding, James J; Venneti, Sriram et al. (2018) In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine. Radiology 287:667-675
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
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
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
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
Shrestha, Liza; Patel, Hardik J; Kang, Yanlong et al. (2017) Copper Mediated Coupling of 2-(Piperazine)-pyrimidine Iodides with Aryl Thiols using Cu(I)Thiophene-2-carboxylate. Tetrahedron Lett 58:4525-4531
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
Weidenauer, Lorenz; Wang, Tai; Joshi, Suhasini et al. (2017) Proteomic interrogation of HSP90 and insights for medical research. Expert Rev Proteomics 14:1105-1117

Showing the most recent 10 out of 191 publications