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Redirecting effector T cells through their IL-2 receptors
J Lustgarten1, J Marks, L A Sherman
1Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|January 14, 1999
Summary
A novel fusion protein, neu-Ab-IL-2, enhances T cell-mediated tumor cell killing. This immunotherapy redirects non-tumor-specific T cells to eliminate Her-2/neu expressing tumors, offering a new strategy for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Fusion proteins linking antibodies to IL-2 (Ab-IL-2) deliver cytokines to tumors.
- These molecules activate and expand antitumor effector cells.
Purpose of the Study:
- To enhance cytolytic activity of CTLs against Her-2/neu tumor antigens.
- To investigate the efficacy of a novel neu-Ab-IL-2 fusion protein.
Main Methods:
- Constructed a fusion protein (neu-Ab-IL-2) of a Her-2/neu-specific antibody and IL-2.
- Assessed tumor cell lysis by Her-2/neu-specific CTLs and non-tumor-specific T cells in vitro.
- Utilized an adoptive transfer model in SCID mice to evaluate in vivo tumor eradication.
Main Results:
- Neu-Ab-IL-2 augmented lysis of Her-2/neu expressing tumor cells by specific CTLs.
- The fusion protein induced lysis by non-tumor-specific T cells via Fas-Fas ligand pathway.
- Neu-Ab-IL-2 facilitated tumor cell elimination in vivo and delayed tumor growth.
Conclusions:
- Neu-Ab-IL-2 enhances T cell-mediated tumor cell killing.
- This fusion protein represents a novel approach to redirect non-tumor-specific T cells for tumor elimination.