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

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, co‐valently 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 antigen‐specific T cells, leading to efficient maintenance of the anti‐tumor activity of adoptively transferred T cells. Int. J. Cancer 82:569–573, 1999. © 1999 Wiley‐Liss, Inc.

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