Antigen-specific cytotoxicity and cell number of adoptively transferred T cells are efficiently maintained in vivo by re-stimulation with an antigen/interleukin-2 fusion protein
✍ Scribed by Bok Y. Kang; Young S. Lim; Su W. Chung; Eui J. Kim; Seung H. Kim; Seung Y. Hwang; Tae S. Kim
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 128 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
In order to maintain in vivo anti-tumor efficacy of antigen (Ag)-specific T cells in adoptive immunotherapy for a prolonged period, we constructed a fusion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor Ag, covalently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produced in a baculovirus expression system displayed potent IL-2 bio-activity. Immunization with the OVA/ IL-2 protein after adoptive transfer of OVA-specific T cells maintained the OVA-specific cytotoxicity and cell number of adoptively transferred T cells long term in vivo, while a simple mixture of recombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the injection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-stimulation of adoptively transferred OVA-specific T cells with the OVA/ IL-2 protein cured 70% of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival period of tumor-bearing mice. These studies suggest that the co-valent linkage between IL-2 and antigen confines the effect of IL-2 to antigenspecific T cells, leading to efficient maintenance of the anti-tumor activity of adoptively transferred T cells.