title: TGFα-PE38 enhances cytotoxic T-lymphocyte killing of breast cancer cells.
abstract: The aim of the present study was to determine whether the combination of two modalities of immunotherapy, targeting two different tumor antigens, may be feasible and non-toxic, yet enhance the killing of a human breast cancer cell line. The first modality was tumor growth factor α-Pseudomonasexotoxin 38 (TGFα-PE38), which specifically targets and kills tumor cells that express the epidermal growth factor receptor. The second modality was mucin-1 (MUC1)-specific cytotoxic T lymphocytes (CTLs), generated by MUC1 stimulation of peripheral blood mononuclear cells, to target the human breast cancer cell line, MCF7. TGFα-PE38 exhibited specific lysis of the MCF7 cells in a concentration- and time-dependent manner. TGFα-PE38 did not kill the normal hematopoietic stem cells or CTLs. Furthermore, TGFα-PE38 was not inhibitory for the growth or differentiation of the normal human hematopoietic stem cells into erythroid and myeloid colonies. In addition, TGFα-PE38 did not inhibit the killing function of CTLs, either when preincubated or co-incubated with CTLs. Finally, therapeutic enhancement was observed, in that TGFα-PE38 and CTLs were additive in the specific lysis of the MCF7 cells. These two modalities of immunotherapy may be beneficial for humans with breast cancer with or without other therapies, including autologous hematopoietic stem cell transplantation, specifically for purging cancer cells from hematopoietic stem cells prior to transplantation.
authors.affiliation: Women's Health Research Institute, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA ; Department of Microbiology and Immunology, School of Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA ; Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA ; Harrington Cancer Center, Amarillo, TX 79106, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Wright
authors.affiliation: Women's Health Research Institute, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Rewers-Felkins
authors.affiliation: Women's Health Research Institute, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Imelda
authors.initials: I
authors.lastname: Quinlin
authors.affiliation: Women's Health Research Institute, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Nazrul I
authors.initials: NI
authors.lastname: Chowdhury
authors.affiliation: Women's Health Research Institute, Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Jewel
authors.initials: J
authors.lastname: Ahmed
authors.affiliation: Harrington Cancer Center, Amarillo, TX 79106, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Eldridge
authors.affiliation: Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Srivastava
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
keywords: TGFα-PE38; breast; cancer; cytotoxic T lymphocyte; mucin-1