Research Landing

Laboratory of Immunologic Monitoring

The Laboratory of Immunologic Monitoring (IML) measures patients' immune responses to different anti-cancer immunotherapy interventions, such as experimental cancer vaccines, to assess their effectiveness. Highly-sophisticated polychromatic flow cytometry techniques allow investigators to measure anti-tumor immune responses on a cellular level. The results help researchers refine their studies and thus improve immunotherapy strategies. Keith Bahjat, Ph.D., and his team are among the nation’s leaders in the effort to develop optimal procedures for monitoring cancer patients' responses to immunotherapy.

Current Projects
The Laboratory of Immunologic Monitoring is engaged in ongoing studies to optimize and use 10-15 parameter polychromatic flow cytometry assays to monitor anti-tumor immune response in cancer patients enrolled in several immunotherapy clinical trials.  These assay procedures simultaneously delineate Ki67+ proliferating memory and effector CD4+ and CD8+ T cells and Treg subpopulations from a single sample of cryopreserved PBMCs.  Assay procedures are also under development to similarly interrogate whole blood samples by direct ex vivo analysis for tumor-activated T cell and Treg subpopulations. 

Additionally, research in the IML  is directed at the correlated resolution of the tumor antigen specific functional response of T cells with polychromatic memory and effector Treg subphenotype signatures.  These assays entail the direct ex vivo analysis of CD107 and/or IFN-γ, IL-17 and IL-2 cytokine responses from patient whole blood or PBMCs; similar combined phenotype and functional polychromatic flow cytometry assays are carried out after brief (4-6 hour) in vitro stimulation with autologous tumor cells or cognate tumor antigen.  This type of more comprehensive immunomonitoring is currently underway for cancer patients being treated with agonist anti-human OX-40 mAb therapy, blocking anti-human CTLA-4 mAb therapy, Treg depletion and adoptive T cell therapy, and for patients receiving combined stereotactic body radiation and IL-2 therapy.

Ongoing studies in the laboratory are focused on the in vitro effects of IL-15 and IL-21 on the proliferation and maintenance of tumor antigen-specific central memory (Tcm) and effector memory (Tem) CD8+ T cells in both murine and human cells. In vivo translational studies in murine tumor models will emphasize the analysis and optimization of combined tumor antigen specific immunization and either IL-21 or IL-15 cytokine therapy in tumor-bearing lymphopenic mice.  Other translational animal research studies pertain to the optimization of procedures for the improved in vivo mobilization of tumor associated antigen, and the subsequent stimulation of tumor antigen directed cross activation of CD8+ cytolytic T cells.  These experiments are carried out in collaboration with the research group of Emmanuel T. Akporiaye, Ph.D.

Patents
Walker, EB, and Sowell, G. Methods of Modulating Dendritic Cells Using Adjuvants.  Serial No.: 60/220,081; Filed: July 21, 2000.

Current Research Collaborations
OX40
Phase I Trial of a Monoclonal Antibody to OX40 in Patients with Advanced Cancer (R01CA109563; PI Brendan Curti, M.D.)
  • Clinical:
    • Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
    • Brendan Curti, M.D., director of genitourinary oncology research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
  • Lab:
    • Andrew Weinberg, Ph.D., Laboratory of Basic Immunology Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center

Melanoma
Exploiting Lymphopenia to Augment the Adoptive Immunotherapy of Melanoma Patients (RO1 CA119123, P.I. Bernard Fox, Ph.D.)

  • Clinical:
    • Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
  • Lab:
    • Hong-Ming Hu, Ph.D., Laboratory of Cancer Immunobiology, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center

Adoptive Cellular Therapy in Melanoma

  • Clinical:
    • Walter J. Urba, M.D., Ph.D., Director Cancer Research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
    • Brendan Curti, M.D., Director of Genitourinary Oncology Research Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
  • Lab:
    • Hong-Ming Hu, Ph.D., Laboratory of Cancer Immunobiology Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center

NSCLC
Clinical Trial of Dribble Vaccine in NSCLC (R21 CA123864 pending PI: Walter Urba, M.D., Ph.D.)

  • Clinical:
    • Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
  • Lab:
    • Bernard A. Fox, Ph.D., Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
    • Hong-Ming Hu, Ph.D., Laboratory of Cancer Immunobiology Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center

Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC

Prostate
Prostate Development of effective immunotherapy for prostate cancer patients (DOD PC020094 – PI: Bernard A. Fox, Ph.D.)

  • Clinical:
    • Brendan Curti, M.D., director of genitourinary oncology research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center

Exploiting lymphopenia and depletion of CD25+ regulatory T cells to augment effective immunotherapy (Prostate Cancer Foundation – PI: Bernard A. Fox, Ph.D.).

  • Clinical: 
    • Walter J. Urba, M.D., Ph.D., director cancer research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center
    • Brendan Curti, M.D., director of genitourinary oncology research, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center  
Full List of Publications

Laboratory Team
Keith S. Bahjat, Ph.D.
Iliana Gonzalez
Daniel Haley
Gwen Kramer
Tanisha Meeuwsen
William Miller