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 f usion protein (OVA/IL-2) containing ovalbumin (OVA) as a model tumor ng, co valently linked to murine interleukin-2 (IL-2). The OVA/IL-2 protein produc ed in a baculovirus expression system displayed potent IL-2 bio-activity. I mmunization with the OVA/IL-2 protein after adoptive transfer of OVA-specif ic T cells maintained the OVA-specific cytotoxicity and cell number of adop tively transferred T cells long term in vivo, while a simple mixture of rec ombinant OVA (rOVA) and rIL-2 did not. The response was dependent on the in jection doses and times of the OVA/IL-2 protein. Furthermore, weekly re-sti mulation of adoptively transferred OVA-specific T cells with the OVA/IL-2 p rotein cured 70% of tumor-bearing mice. In contrast, re-stimulation with a mixture of rOVA and rIL-2 could not significantly prolong the survival peri od 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 adopt ively transferred T cells. (C) 1999 Wiley-Liss, Inc.