Administration of BiMAb-retargeted T cells in a rat hepatic metastases colon tumour model results in T-cell tumour infiltration independent of the route of administration.
In this study, cultured T cells, pre-incubated with the bispecific monoclonal antibody (BiMAb) R73IgG1 x CC52IgG1 were adoptively transferred, via systemic and regional routes, to rats bearing day 10 hepatic metastases of the CC531 adenocarcinoma of the colon to investigate the role of the route of administration in tumour infiltration by these BiMAb-retargeted effector cells. The BiMAb, directed against the T-cell receptor and the tumour-associated antigen CC52, were used to crosslink CC531 tumour cells and T cells to induce tumour cell lysis. Retargeted T cells were administered via the jugular vein, hepatic artery or the portal vein. The number of BiMAb-retargeted T cells that reached the liver tumours was independent of the route of administration. There was also no difference between the number of T cells that reached the portal tracts, central veins of parenchyma of the liver, after loco-regional or systemic administration. These findings are in contrast to the interleukin (IL)-2 activated NK (A-NK) cells biodistribution studies earlier performed in the same animal model in our laboratory. Compared with A-NK cells, a lower number of BiMAb-retargeted T cells reached the tumours, irrespective of their route of administration while for A-NK cells, there was an advantage of administration via the hepatic artery.
Koelemij
R
R
Department of Surgery, Leiden University Medical Centre, K6-R, P.O. Box 9600, 2300 RC Leiden, The Netherlands. koelemij@knmg.nl
Hagenaars
M
M
Ensink
N G
NG
Eggermont
A M
AM
Van De Velde
C J
CJ
Fleuren
G J
GJ
Kuppen
P J
PJ
D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000556:secondary; D019264:Adoptive Transfer; D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000276:immunology*; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007601:Jugular Veins; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal