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.
Kang
B Y
BY
College of Pharmacy and Institute of Drug Development, Chonnam National University, Kwangju, Republic of Korea.
Lim
Y S
YS
Chung
S W
SW
Kim
E J
EJ
Kim
S H
SH
Hwang
S Y
SY
Kim
T S
TS
D000818:Animals; D002452:Cell Count; D000939:Epitopes / Q000627:therapeutic use*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000637:transplantation*
D000939:Epitopes; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin