Paul C Tumeh

Publications of Paul C Tumeh

• The impact of ex vivo clinical grade activation protocols on human T-cell phenotype and function for the generation of genetically modified cells for adoptive cell transfer therapy.

  Authors: Paul C Tumeh, Richard C Koya, Thinle Chodon, Nicholas A Graham, Thomas G Graeber, Begoña Comin-Anduix, Antoni Ribas

  Journal of immunotherapy (Hagerstown, Md. : 1997). 10/2010; 33(8):759-68.

  Optimized conditions for the ex vivo activation, genetic manipulation, and expansion of human lymphocytes for adoptive cell therapy may lead to protocols that maximize their in vivo function. WeOptimized conditions for the ex vivo activation, genetic manipulation, and expansion of human lymphocytes for adoptive cell therapy may lead to protocols that maximize their in vivo function. We analyzed the effects of 4 clinical grade activation and expansion protocols over 3 weeks on cell proliferative rate, immunophenotype, cell metabolism, and transduction efficiency of human peripheral blood mononuclear cells (PBMCs). Peak lentiviral transduction efficiency was early (days 2 to 4), at a time when cells showed a larger size, maximal uptake of metabolic substrates, and the highest level of proximal T-cell receptor signaling engagement. Anti-CD2/3/28 activation beads induced greater proliferation rate and skewed PBMCs early on to a CD4 phenotype when compared with the cells cultured in OKT3. Multicolor surface phenotyping demonstrated that changes in T-cell surface markers that define T-cell functional phenotypes were dependent on the time spent in culture as opposed to the particular activation protocol. In conclusion, ex vivo activation of human PBMCs for adoptive cell therapy demonstrate defined immunophenotypic and functional signatures over time, with cells early on showing larger sizes, higher transduction efficiency, maximal metabolic activity, and zeta-chain-associated protein-70 activation.

• PET imaging of cancer immunotherapy.

  Authors: Paul C Tumeh, Caius G Radu, Antoni Ribas

  Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 07/2008; 49(6):865-8.

  Immune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells andImmune system activation can be elicited in viral infections, active immunization, or cancer immunotherapy, leading to the final common phenotype of increased glycolytic use by immune cells and subsequent detection by 18F-FDG PET. Because 18F-FDG is also used in baseline staging PET/CT scans and in tumor response assessment, physicians are faced with a unique challenge when evaluating tumor response in patients receiving cancer immunotherapy. The burgeoning field of cancer immunotherapy and the paucity of PET probes that can reliably differentiate activated immune cells from metabolically active cancer cells underscore the pressing need to identify and develop additional molecular imaging strategies. In an effort to address this concern, investigators have taken several molecular imaging approaches for cancer immunotherapy. Direct ex vivo labeling of T lymphocytes with radioactive probes before reinfusion represents the earliest attempts but has proven to be clinically limited because of significant PET probe dilution from proliferation of activated immune cells. Another approach is the indirect in vivo labeling of immune cells via PET reporter gene expression and involves the ex vivo genetic engineering of T lymphocytes with a reporter gene, reinfusion into the host, and the subsequent use of a PET probe specific for the reporter gene. The most recent approach involves the direct in vivo labeling of immune cells by targeting endogenous immune cell biochemical pathways that are differentially expressed during activation. In conclusion, these novel PET-based imaging approaches have demonstrated promise toward the goal of in vivo, noninvasive immune monitoring strategies for evaluating cancer immunotherapy.

• Differentiation of vascular and non-vascular skin spectral signatures using in vivo hyperspectral radiometric imaging: implications for monitoring angiogenesis.

  Authors: Paul C Tumeh, Jeremy M Lerner, David T Dicker, Wafik S El-Deiry

  Cancer biology & therapy. 04/2007; 6(3):447-53.

  Molecular imaging techniques can detect and monitor characteristics of the tumor microenvironment, such as angiogenesis, hypoxia, metabolism, and apoptosis that may better correlate with response toMolecular imaging techniques can detect and monitor characteristics of the tumor microenvironment, such as angiogenesis, hypoxia, metabolism, and apoptosis that may better correlate with response to cancer therapy and may provide information in real-time. We investigated the use of a novel, spatially discrete, hyperspectral, multi-fiber optical system to characterize selected regions of skin in living mice. We determined the reproducibility and robustness of the spectral signatures derived from comparable regions of interest. Additionally, we characterized spectral differences in vascular and non-vascular fields to determine their potential use in monitoring angiogenesis. The macroscopic Prism and Reflectance Imaging Spectroscopy System (MACRO-PARISS) was calibrated against a National Institute for Standards and Technology (NIST)-certified lamp, allowing for reproducible spectra with any instrument similarly calibrated. Spectra were classified using a linearity-independent algorithm over a wavelength range of 450-920 nm. Classified spectra were integrated into a spectral library and subsequent acquisitions were correlated with the library set to a minimum correlation coefficient (MCC) of 99%. The results indicated that similar regions of interest with respect to vascularity consistently generated a unique spectral signature. As the field of view (FOV) moved from vascular to non-vascular areas, the acquired spectra changed in a step-wise and predictable fashion. Additionally, vascular fields that were deprived of their blood supply subsequently generated a non-vascular spectral signature. This work has implications for the monitoring of various physiologic or pathological processes including tumor angiogenesis and the therapeutic effects of anti-vascular agents.

• Structural and functional imaging correlates for age-related changes in the brain.

  Authors: Paul C Tumeh, Abass Alavi, Mohamed Houseni, Antje Greenfield, Timothy Chryssikos, Andrew Newberg, Drew A Torigian, Gul Moonis

  Seminars in nuclear medicine. 04/2007; 37(2):69-87.

  In recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonanceIn recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonance (MR) imaging, advanced MR techniques, and functional MR imaging. This review summarizes the latest advances in understanding physiologic maturation and aging as detected by these neuroimaging modalities. We also present our experience with MR volumetric and positron emission tomography analysis in separate cohorts of healthy subjects in the pediatric and adult age groups respectively. Our results are consistent with previous studies and include the following: total brain volume was found to increase with age (up to 20 years of age). Whole brain metabolism and frontal lobe metabolism both decrease significantly with age (38% and 42%, respectively), whereas cerebellar metabolism does not show a significant decline with age. Defining normal alterations in brain function and structure allows early detection of disorders such as Alzheimer's and Parkinson's diseases, which are commonly associated with normal aging.