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
By. Kang et al., 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, INT J CANC, 82(4), 1999, pp. 569-573
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.