Adoptive immunotherapy by avidin-driven cytotoxic T lymphocyte-tumor bridging.
We have shown previously that T cells, tagged with biotinylated anti-CD3 antibody fragments, can exert avidin-dependent cytolytic activity on suitably biotinylated tumor cells in vitro. In this study, we demonstrate that avidin-driven CTL-tumor bridging in vivo leads to growth inhibition of murine tumors WEHI-164 fibrosarcoma and RMA lymphoma. The biodistribution of biotin-tagged 111In-labeled T cells demonstrated a selective avidin-dependent and time-dependent accumulation of radioactivity at tumor sites. The specificity of lymphocyte tumor localization was demonstrated by the concurrent time-dependent decrease of radioactivity in the blood and in all other organs. Furthermore, we documented a therapeutic effect of the adoptively transferred T cells, i.e., a significant delay of tumor growth at early stages. All of the experiments included a control group of mice, which received all of the reagents, except avidin. These avidin-minus mice showed no specific localization and no delay in tumor growth, indicating that avidin bridging was essential for T-cell activity at tumor sites.
Guttinger
M
M
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.
Guidi
F
F
Chinol
M
M
Reali
E
E
Veglia
F
F
Viale
G
G
Paganelli
G
G
Corti
A
A
Siccardi
A G
AG
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001360:Avidin / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism*; D019921:Biotinylation; D017252:CD3 Complex / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D001360:Avidin; D001710:Biotin