Abstract

Hepatocellular cancer (HCC), with a global annual incidence of about 1.2 million new cases, represents one of the largest causes of cancer death in the world. Surgery is the only effective treatment and is available to and benefits only a very small minority of patients. No significant advances in the treatment of HCC have been made in the last two decades. Most HCC produce alpha fetoprotein (AFP), a 609 amino acid residue tumor marker. The applicants hypothesize that short AFP peptides, processed and presented by major histocompatibility class (MHC) molecules on the surface of HCC cells, can serve as suitable targets for an effective cell-mediated immune response against this tumor. They hypothesize that the human and murine T-cell repertoires have AFP peptide-responsive T cells that can be clonally expanded and activated under proper conditions. They propose a multipronged strategy with three Specific Aims to test this hypothesis with both murine and human HCC models.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA077623-02
Application #
2896452
Study Section
Special Emphasis Panel (ZRG2-ET-1 (02))
Program Officer
Hecht, Toby T
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Butterfield, Lisa H; Ribas, Antoni; Potter, Douglas M et al. (2007) Spontaneous and vaccine induced AFP-specific T cell phenotypes in subjects with AFP-positive hepatocellular cancer. Cancer Immunol Immunother 56:1931-43
Schumacher, Lana Y; Vo, Dan D; Garban, Hermes J et al. (2006) Immunosensitization of tumor cells to dendritic cell-activated immune responses with the proteasome inhibitor bortezomib (PS-341, Velcade). J Immunol 176:4757-65
Butterfield, Lisa H; Ribas, Antoni; Dissette, Vivian B et al. (2006) A phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four alpha-fetoprotein peptides. Clin Cancer Res 12:2817-25
Ribas, Antoni; Vo, Dan D; Weeks, David L et al. (2006) Broad antitumor protection by dendritic cells administered to CD8alpha knock out mice. Cancer Immunol Immunother 55:663-71
Wargo, Jennifer A; Schumacher, Lana Y; Comin-Anduix, Begonya et al. (2005) Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells. Cancer Gene Ther 12:516-27
Ribas, Antoni; Wargo, Jennifer A; Comin-Anduix, Begonya et al. (2004) Enhanced tumor responses to dendritic cells in the absence of CD8-positive cells. J Immunol 172:4762-9
Mehrotra, Shikhar; Chhabra, Arvind; Chakraborty, Abolokita et al. (2004) Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells. Immunology 113:472-81
Ribas, Antoni; Glaspy, John A; Lee, Yohan et al. (2004) Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J Immunother 27:354-67
Schumacher, Lana; Ribas, Antoni; Dissette, Vivian B et al. (2004) Human dendritic cell maturation by adenovirus transduction enhances tumor antigen-specific T-cell responses. J Immunother 27:191-200
Mehrotra, Shikhar; Stevens, Robert; Zengou, Ryan et al. (2003) Regulation of melanoma epitope-specific cytolytic T lymphocyte response by immature and activated dendritic cells, in vitro. Cancer Res 63:5607-14

Showing the most recent 10 out of 28 publications