Our group has demonstrated the clinical promise of a whole-cell vaccine composed of irradiated but viable melanoma cells from three human melanoma cell lines (M10, M24, and M101). Because melanoma cells also can express receptors for cytokines currently used in invitro expansion and activation of dendritic cells, we hypothesized that the efficacy of a human whole-cell melanoma vaccine could be significantly increased by using these cytokines to upregulate vaccine expression of costimulatory molecules. This study's objective is to demonstrate the induction of significant immune responses in patients receiving a cytokine- modified M24 whole-cell vaccine for treatment of regional or distant metastatic melanoma. There are three specific aims: 1. To determine whether certain cytokines such as interleukin 4, granuloctye macrophage-colony stimulating factor, and tumor necrosis factor-alpha can upregulate expression of multiple costimulatory molecules (CD54, CD58, CD80, and CD86) on human melanoma cells. 2. To determine how the coexpression of multiple costimulatory molecules and tumor antigens on melanoma cells affects the activation of T cells, the induction of autologous tumor-specific cellular cytotoxicity, and induction of specific cytotoxic T cells against MAGE1, MAGE3, and tyrosinase peptide epitopes. 3. To determine if administration of a cytokine- modified melanoma cell vaccine can induce significant immunological responses, specifically delayed-type hypersensitivity, cellular cytotoxicity, and complement-dependent cytotoxicity, in HLA haplotype-matched melanoma patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08CA087071-02
Application #
6377992
Study Section
Subcommittee G - Education (NCI)
Program Officer
Myrick, Dorkina C
Project Start
2000-08-01
Project End
2005-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$129,600
Indirect Cost
Name
John Wayne Cancer Institute
Department
Type
DUNS #
556074458
City
Santa Monica
State
CA
Country
United States
Zip Code
90404