This proposal describes a phase I clinical trial using tumor antigen specific cytotoxic T-lymphocytes (CTLs) as adoptive immunotherapy for patients with recurrent chemotherapy-resistant ovarian cancer. In this trial, subjects will undergo leukopheresis for collection of precursor lymphocytes. These precursor cells will then be stimulated and expanded in culture in the presence of MUC1, a mucin antigen specific to several malignant human cells, including ovarian cancer. The resulting CTLs will then be administered to the subject via intraperitoneal infusion. It is hypothesized that these ex-vivo generated, tumor-specific CTLs will overcome normal tumor-induced host immunosuppression and initiate effective tumor cell killing, with minimal toxicity.
The specific aims of the trial are 1) to determine the toxicity and feasibility of the use of intraperitoneal infusions of tumor specific CTLs; 2) to determine the migration pattern/distribution of the CTLs by use of 111-Indium radioisotope labeling; 3) to determine if repetitive cycles of CTL generation and infusion progressively increase the measurable ovarian cancer specific activity; and 4) to observe clinical response of patients receiving MUC1-specific CTL, and if possible, correlate response to migration patterns and to the level of ovarian cancer specific activity generated by the CTLs. The longer-term goal of this trial is to serve as a basis for larger scale testing of the therapeutic effect of this technique, and ultimately to develop a new treatment modality for ovarian cancer that may be used alone or in combination with existing methods to improve outcome.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA089883-01A1
Application #
6401983
Study Section
Special Emphasis Panel (ZRG1-CONC (01))
Program Officer
Wu, Roy S
Project Start
2001-09-12
Project End
2003-08-31
Budget Start
2001-09-12
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$195,750
Indirect Cost
Name
Don and Sybil Harrington Cancer Center
Department
Type
DUNS #
City
Amarillo
State
TX
Country
United States
Zip Code
79118
Wright, Stephen E (2012) Immunotherapy of breast cancer. Expert Opin Biol Ther 12:479-90
Wright, Stephen E; Rewers-Felkins, Kathleen A; Quinlin, Imelda S et al. (2012) Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study. J Immunother 35:196-204
Dobrzanski, Mark J; Rewers-Felkins, Kathleen A; Samad, Khaliquzzaman A et al. (2012) Immunotherapy with IL-10- and IFN-ýý-producing CD4 effector cells modulate ""Natural"" and ""Inducible"" CD4 TReg cell subpopulation levels: observations in four cases of patients with ovarian cancer. Cancer Immunol Immunother 61:839-54
Dobrzanski, Mark J; Rewers-Felkins, Kathleen A; Quinlin, Imelda S et al. (2009) Autologous MUC1-specific Th1 effector cell immunotherapy induces differential levels of systemic TReg cell subpopulations that result in increased ovarian cancer patient survival. Clin Immunol 133:333-52
Wright, Stephen E; Rewers-Felkins, Kathleen A; Quinlin, Imelda S et al. (2008) MHC-unrestricted lysis of MUC1-expressing cells by human peripheral blood mononuclear cells. Immunol Invest 37:215-25