Dendritic cells armed with anti-CD3 mAbs reduce pulmonary metastases, prolong survival, and engender antitumor effector cells demonstrable by adoptive transfer

Mary A. Maluccio, Jyosthna Rao, Vijay Sharma, Milagros Lagman, Manikkam Suthanthiran

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Abstract

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)771-776
Number of pages6
JournalAnnals of Surgical Oncology
Volume7
Issue number10
DOIs
Publication statusPublished - 1 Jan 2000

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Keywords

  • Anti-CD3 mAbs
  • Dendritic cells
  • Tumor immunotherapy

ASJC Scopus subject areas

  • Surgery
  • Oncology

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