The Immunology and Immunotherapy (l&l) Program represents the merger of the central components of two pre-existing programs, the basic science Immunology Program and the immunotherapy-oriented Lymphoma Program. The l&l Program's overall mission is to translate fundamental advances in our understanding of basic cancer immunology to therapeutic advances, by closely coordinating and integrating the laboratory and clinical components. This coordination is highly bidirectional, however. Insights gained in the laboratory used to inform the development of new therapies, and discoveries in the clinic are used to direct new laboratory studies. The l&l Program is built upon an exceptionally strong foundation in fundamental immunology, its members comprising an illustrious group of investigators responsible for major advances in T- and B-cell development, dendritic cell function, Toll-like receptors, and antigen presentation. Moreover, the l&l Program has produced a variety of novel immunotherapeutic approaches, encompassing a spectrum of immunologic strategies facilitated by the Program's laboratory advances, including 1) the induction of anti-tumor immunity via extracorporeal photoimmunetherapy (ECP);2) methods of minimizing graft-versus-host disease in allogeneic stem cell transplantation;3) optimization of graft-versus-tumor responses;4) biodegradable nanoparticles for delivery of tumor antigen vaccines;5) enhancement of anti-tumor immune responses by blockade of CTLA-4. The l&l Program has 46 independent but highly interactive members representing both laboratory and clinical investigators from 11 departments. The program is led by Ira Mellman (Chair, Cell Biology;YCC Associate Director for Science), bridges the fundamental and clinical l&l components. Dr. Mellman is an expert in the mechanisms of antigen presentation by DCs and more recently has focused on applying basic immunological principles to the development of human cancer immunotherapies. Three Associate Leaders, working closely with Dr. Mellman, direct subcomponents of the Program. Dr. Warren Shlomchik oversees the basic cancer immunology component, while Dr. Michael Girardi and Dr. Francine Foss have responsibility for the immunotherapy component. Communication and programmatic focus are maintained by a monthly meeting of members devoted to cancer immunology, a working group charged with implementing immunotherapy protocols, a general retreat, a seminar series, and a newly established seed grant competition to fund innovative approaches to immunotherapy. Total peer-reviewed support is $20.8 direct costs ($30.1 million total costs). Overall funding is $28.4 million in direct costs ($39.2 million total costs). In the last grant period, 613 cancerrelated papers were published, of which 23% were intraprogrammatic and 11% were interprogrammatic.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA016359-33
Application #
8312352
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
33
Fiscal Year
2011
Total Cost
$29,455
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Sanmamed, Miguel F; Chen, Lieping (2018) A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 175:313-326
Gupta, Swati; Mani, Navin R; Carvajal-Hausdorf, Daniel E et al. (2018) Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer. Lab Invest 98:1076-1083
Bellone, Stefania; Buza, Natalia; Choi, Jungmin et al. (2018) Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement. Clin Cancer Res 24:3282-3291
Altan, Mehmet; Kidwell, Kelley M; Pelekanou, Vasiliki et al. (2018) Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer. NPJ Breast Cancer 4:40
Kim, Tae Kon; Herbst, Roy S; Chen, Lieping (2018) Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends Immunol 39:624-631
Goldberg, Sarah B; Patel, Abhijit A (2018) Monitoring immunotherapy outcomes with circulating tumor DNA. Immunotherapy 10:1023-1025
Wang, Shi-Yi; Long, Jessica B; Killelea, Brigid K et al. (2018) Associations of preoperative breast magnetic resonance imaging with subsequent mastectomy and breast cancer mortality. Breast Cancer Res Treat 172:453-461
Bonazzoli, Elena; Predolini, Federica; Cocco, Emiliano et al. (2018) Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clin Cancer Res 24:4845-4853
Villarroel-Espindola, Franz; Yu, Xiaoqing; Datar, Ila et al. (2018) Spatially Resolved and Quantitative Analysis of VISTA/PD-1H as a Novel Immunotherapy Target in Human Non-Small Cell Lung Cancer. Clin Cancer Res 24:1562-1573
Wadia, Roxanne J; Stolar, Marilyn; Grens, Clarice et al. (2018) The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients. Oncotarget 9:7322-7331

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