Dendritic cells armed with anti-CD3 mAbs reduce pulmonary metastases, prolong survival, and engender antitumor effector cells demonstrable by adoptive transfer.
BACKGROUND
Dendritic cells (DCs) pulsed with tumor cells or peptides are effective antitumor agents in a number of tumor models. In light of our earlier demonstration that T-cell signaling via the CD3 proteins induces cytolytic activity and constrains tumor progression, we equipped DCs pulsed with tumor cells with anti-CD3 mAbs and tested their antitumor efficacy in a murine renal cell cancer pulmonary metastasis model.


METHODS
We investigated the antitumor efficacy of DCs pulsed with whole irradiated tumor cells (DC/R) or DCs pulsed with irradiated tumor cells and armed with anti-CD3 mAbs (DC/R/anti-CD3 mAbs). Experimental end points included the number of pulmonary metastases and survival of tumor-inoculated mice.


RESULTS
Our studies demonstrate that arming tumor-pulsed DCs with anti-CD3 mAbs results in a superior outcome compared to that from tumor-pulsed DCs alone in terms of reduction in the number of pulmonary metastases and survival times. Furthermore, adoptive transfer experiments revealed that the splenocytes from DC/R/anti-CD3 mAbs-treated mice are superior to splenocytes from DC/R-treated mice in reducing renal cancer pulmonary metastases in severe combined immunodeficient (SCID) beige mice.


CONCLUSIONS
Our data suggest that the therapeutic efficacy of DCs pulsed with tumor cells can be augmented by arming them with anti-CD3 mAbs. DC-based treatment regimens that currently are being pursued in clinical trials might be improved by equipping such cells with anti-CD3 mAbs.
Maluccio
M A
MA
Department of Surgery, New York Presbyterian Hospital/Weill Medical College of Cornell University, New York 10021, USA.
Rao
J
J
Sharma
V
V
Lagman
M
M
Suthanthiran
M
M
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D003713:Dendritic Cells; D016219:Immunotherapy, Adoptive; D007680:Kidney Neoplasms / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D023421:Models, Animal; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D017252:CD3 Complex