The development of therapies activating the cellular immune system (immunotherapy) is one of the fastest growing areas of cancer treatment. A critical part of clinical trials testing new immunotherapies, such as vaccines against tumor antigens, is monitoring tumor-specific immune responses to validate whether we are actually targeting and activating specific leukocyte subsets as intended, and whether immune activation correlates with clinical outcome. In addition, proper interpretation of the results of these immune response assays is needed to find ways of optimizing immunotherapies for future clinical trials. UT MD Anderson Cancer Center has recently established an immune monitoring core laboratory (IMCL) at its South Campus as part of the expansion of its immunotherapy program in cancer. This core laboratory houses a number of key technologies and infrastructure needed to support both clinical and pre-clinical assessment of T-cell and ARC function in cancer patients, including blood and tumor processing and storage, cell culture tools for in vitro stimulation, flow cytometry, and measurement of antigen-specific T-cell function using cytokine and CTL assays. We are also developing new and more sensitive T-cell assay technologies and have recently launched a new highly-sensitive non-radioactive CTL assay.
The aim of the IMCL will be to support both preclinical and clinical aspects of all projects in this PO1 grant. Throughout the PO1 grant period, the IMCL will work with all the PO1 Projects by assisting in blood and tissue processing and will help develop multicolor flow cytometry and cellular assays to characterize the effects of pDC on anti-tumor T cell phenotype and function. One of our main activities will be to perform the immune monitoring in the clinical trial of Project 4 that will test the effects of TLR7 and TLR8 agonists during gplOO and MAGE-3 peptide vaccination in melanoma patients. The IMCL will process all peripheral blood mononuclear cell samples and tumor biopsies from this trial, establish a specimen storage bank, and develop an electronic specimen database during the clinical trial (Month 6 to Year 4.5 -Mpt/mo). In Year 1 we will work with Project 4 in optimizing and validating T-cell phenotypic and functional assays that will be used in Year 5 of the grant period to monitor the antigenspecific T cell responses in patients enrolled on the clinical trial. All immune monitoring measurements will be analyzed in collaboration with the Biostatistics and Data Management Core (Core C).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA128913-04
Application #
8332334
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$487,433
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Huang, L; Wang, Z; Liu, C et al. (2017) CpG-based immunotherapy impairs antitumor activity of BRAF inhibitors in a B-cell-dependent manner. Oncogene 36:4081-4086
Peng, Weiyi; Chen, Jie Qing; Liu, Chengwen et al. (2016) Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov 6:202-16
Meller, Stephan; Di Domizio, Jeremy; Voo, Kui S et al. (2015) T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol 16:970-9
Singh, Manisha; Overwijk, Willem W (2015) Intratumoral immunotherapy for melanoma. Cancer Immunol Immunother 64:911-21
Lande, Roberto; Chamilos, Georgios; Ganguly, Dipyaman et al. (2015) Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA. Eur J Immunol 45:203-13
Singh, Manisha; Khong, Hiep; Dai, Zhimin et al. (2014) Effective innate and adaptive antimelanoma immunity through localized TLR7/8 activation. J Immunol 193:4722-31
Hailemichael, Yared; Overwijk, Willem W (2013) Peptide-based anticancer vaccines: The making and unmaking of a T-cell graveyard. Oncoimmunology 2:e24743
Radvanyi, Laszlo; Pilon-Thomas, Shari; Peng, Weiyi et al. (2013) Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer--letter. Clin Cancer Res 19:5541
Hailemichael, Yared; Dai, Zhimin; Jaffarzad, Nina et al. (2013) Persistent antigen at vaccination sites induces tumor-specific CD8? T cell sequestration, dysfunction and deletion. Nat Med 19:465-72
Yang, Yan; Liu, Chengwen; Peng, Weiyi et al. (2012) Antitumor T-cell responses contribute to the effects of dasatinib on c-KIT mutant murine mastocytoma and are potentiated by anti-OX40. Blood 120:4533-43

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