University of Pittsburgh Cancer Institute (UPCI)

Lisa Butterfield, PhD

Lisa Butterfield
Professor of Medicine, Surgery and Immunology
Director, Immunologic Monitoring and Cellular Products Laboratory, UPCI

Contact Information

Contact Information

Hillman Cancer Center 1.27
Research Pavilion
5117 Centre Ave.
Pittsburgh, PA 15213

Phone: 412-623-4661
Email: butterfieldl@upmc.edu
Fax: 412-624-0264

Research Keywords

Research Keywords

Immune therapies; viral therapies; cancer vaccines; dendritic cells; immunotherapy; melanoma; hepatocellular carcinoma; alpha-fetoproteins

Research Summary

Research Summary

The Butterfield lab focuses on cross-talk between tumor antigens and the immune system in melanoma and hepatocellular cancer (HCC) patients. We have studied immunodominant and subdominant epitope-specific T cells we identified specific for alpha fetoprotein (AFP), a self antigen expressed by HCC. Immunodominant epitopes have been tested as a vaccine in HCC patients in the form of both peptides in adjuvant, and as peptide-pulsed dendritic cell (DC) vaccines. These vaccines induced increased circulating activated and expanded AFP-specific, IFN-gamma-producing, CD8+ T cells. HCC patients can spontaneously have detectable frequencies of circulating AFP-specific CD8+ T cells to both immunodominant and subdominant epitopes, and these T cells can be differentially expanded with different modes of antigen presentation by DC. Antigen engineered DC (AdVhAFP/DC)-stimulated CD8+ responses are antigenically diverse and not skewed towards subsets of peptides.

In melanoma vaccine trials, we find that frequency and function of vaccine induced MART-1-specific T cells is unrelated to clinical outcome, but that broadening of the immune response (“determinant spreading”) to include additional antigens expressed by tumor is correlated with positive clinical outcome. We have created a 3-melanoma-antigen encoding adenovirus, AdVTMM2, and this virus, transduced into DC, is being tested clinically to determine whether broader immunity is critical to clinical outcome, and whether systemic IFN-alpha can further promote determined spreading, and improved clinical response. Most recently, we are investigating methods for incorporating innate effector (NK cell) activation with tumor antigen-specific adaptive immunity. We find that AdV-transduced DC can activate both major subsets of NK cells, as well as secret chemokines to draw NK cells to the DC. By understanding these immune responses, improved cancer vaccines can be rationally designed that specifically bring many immunologic weapons together, encompassing killer and helper T cells, as well as NK cells, to fight cancer.

Selected Publications

Selected Publications

  • Butterfield, L.H., Ribas, A., Dissette, V.B., Amarnani, S., Vu, H., Oseguera, D.,Wang, H.-J., Elashoff, R.M., McBride, W.H. Mukherji, B., Cochran, A., Glaspy, J.A., and Economou, J.S. Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin. Cancer Res., 9: 998-1008, 2003. PubMed Link
  • Butterfield, L.H., Ribas, A., Dissette, V.B., Lee, Y., Yang, J., De la Rocha, P., Duran, S.D., Hernandez, J., Seja, E., Potter, D.M., McBride, W.H., Finn, R., Glaspy, J.A., and Economou, J.S. A Phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin. Cancer Res., 12: 2817-2825, 2006. PubMed Link
  • Liu, Y., Daley, S., Evdokimova, V.N., Zdobinski, D.D., Potter, D.M., and Butterfield, L.H. Hierarchy of alpha-fetoprotein (AFP)-specific T cell responses in subjects with AFP-positive hepatocellular cancer. J. Immunol., 177: 712-721, 2006. PubMed Link
    Shared Resources Used: BF, CF
  • Butterfield, L.H., Comin-Anduix, B., Vujanovic, L., Lee, Y., Dissette, V.B., Yang, J-Q., Vu, H.T., Seja, E., Oseguera, D.K., Potter, D.M., Glaspy, J.A., Economou, J.S., and Ribas, A. Adenovirus MART-1 engineered autologous dendritic cell vaccine for metastatic melanoma. J. Immunother., 31: 294-309, 2008. PubMed Link
  • Vujanovic, L.N., Szymkowski, D.E., Alber, S., Watkins, S.C., Vujanovic, N.L., and Butterfield, L.H. Virally-infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15. Blood, 116(4):575-583, 2010. PubMed Link
    Shared Resources Used: AF, CF, CTIF
  • Butterfield, L.H., Palucka, A.K., Britten, C.M., Dhodapkar, M.V., Hakansson, L., Janetzki, S., Kawakami, Y., Kleen, T-O., Lee, P.P., Maccalli, C., Maecker, H.T., Maino, V.C., Maio, M., Malyguine, A., Masucci, G., Pawelec, G., Potter, D.M., Rivoltini, L., Salazar, L.G., Schendel, D.J., Slingluff, C.L., Jr., Song, W., Stroncek, D.F., Tahara, H., Thurin, M., Trinchieri, G., van Der Burg, S.H., Whiteside, T.L., Wigginton, J.M., Marincola, F., Khleif, S., Fox, B.A., and Disis, M.L. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers. Clin. Cancer Res., 17(10): 3064-3076, 2011. PubMed Link
    Shared Resources Used: IMCPL
  • Blalock, L.T., Landsberg, J., Messmer, M.N., Shi, J., Pardee, A.D., Haskell, R.E., Vujanovic, L., Kirkwood, J.M., and Butterfield, L.H. Human dendritic cells adenovirally-engineered to express three defined tumor antigens promote broad adaptive and innate immunity. OncoImmunol., 1(3): 1-11, 2012. PubMed Link
    Shared Resources Used: IMCPL
  • Vujanovic, L., Ballard, W., III, Thorne, S.H., Vujanovic, N., and Butterfield, L.H. Adenovirus-engineered human dendritic cells induce natural killer cell chemotaxis via CXCL8/IL-8 and CXCL10/IP-10. OncoImmunol., 1(4):448-457, 2012. PubMed Link
    Shared Resources Used: CF, IMCPL
  • Butterfield, L.H., Potter, D.M., and Kirkwood, J.M. Multiplex serum biomarker assessments: Technical and biostatistical issues. J. Trans. Med., 9: 173, 2011. PubMed Link
    Shared Resources Used: BF, IMCPL
  • Naveh, H.P., Vujanovic L., and Butterfield, L.H. Cellular immunity induced by a recombinant adenovirus- human dendritic cell vaccine for melanoma. J. Immunother. Cancer, 1:19, 2013. PubMed Link
    Shared Resources Used: IMCPL

See all pubs (Pubmed)

Collaborations

Collaborations

Current UPCI/Pitt Collaborators

William Gooding, MS
Senior Biostatistician
Member - Head and Neck Cancer Program (HNCP)

John Kirkwood, MD
Thomas and Sandra Usher Professor of Medicine
Co-Leader - Melanoma Program (MP)

Hideho Okada, MD, PhD
Associate Professor of Neurological Surgery

Ian Pollack, MD
Dr. Walter E. Dandy Professor of Neurological Surgery
Member - Cancer Therapeutics Program (CTP)

Ahmad Tarhini, MD, PhD
Associate Professor of Medicine
Member - Melanoma Program (MP)

Theresa Whiteside, PhD
Professor of Pathology
Member - Cancer Immunology Program (CIP)

Nathan Yates, PhD
Associate Professor of Cell Biology
Member - Molecular and Cellular Cancer Biology Program (MCCBP)

Current External Collaborators

David Stroncek, MD
Chief, Cell Processing Section
National Institutes of Health

UPCI Shared Resource Usage

UPCI Shared Resource Usage

  • Biostatistics Facility
  • Cancer Genomics Facility
  • Cancer Proteomics Facility
  • Cell and Tissue Imaging Facility
  • Cytometry Facility
  • IMCPL

Affiliated Graduate Programs

Department Website

Lab Website









Last modified: 6/10/14