NSU-MD Faculty Articles

Synergy between tumor immunotherapy and antiangiogenic therapy.

Publication Title

Blood

Publisher

American Society of Hematology

ISSN

0006-4971

Publication Date

8-1-2003

Keywords

Animals, Antigens, Neoplasm, Combined Modality Therapy, Dendritic Cells, Endothelial Growth Factors, Female, Immunotherapy, Adoptive, Infertility, Intercellular Signaling Peptides and Proteins, Lymphocyte Activation, Lymphokines, Male, Mice, Mice, Inbred Strains, Neoplasm Proteins, Neoplasms, Experimental, Neovascularization, Pathologic, Proto-Oncogene Proteins, RNA, Neoplasm, Receptor Protein-Tyrosine Kinases, Receptor, TIE-2, T-Lymphocytes, Cytotoxic, Transfection, Treatment Outcome, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factors

Abstract

This study tested the hypothesis that combination of antiangiogenic therapy and tumor immunotherapy of cancer is synergistic. To inhibit angiogenesis, mice were immunized with dendritic cells (DCs) transfected with mRNA that encode products that are preferentially expressed during neoangiogenesis: vascular endothelial growth factor receptor-2 (VEGFR-2) and Tie2 expressed in proliferating endothelial cells, and vascular endothelial growth factor (VEGF) expressed in the angiogenic stroma as well as the tumor cells used in this study. Immunization of mice against VEGF or VEGFR-2 stimulated cytotoxic T lymphocyte (CTL) responses and led to partial inhibition of angiogenesis. Antiangiogenic immunity was not associated with morbidity or mortality except for a transient impact on fertility seen in mice immunized against VEGFR-2, but not VEGF. Tumor growth was significantly inhibited in mice immunized against VEGF, VEGFR-2, and Tie2, either before tumor challenge or in the setting of pre-existing disease in murine B16/F10.9 melanoma and MBT-2 bladder tumor models. Coimmunization of mice against VEGFR-2 or Tie2 and total tumor RNA exhibited a synergistic antitumor effect. Synergism was also observed when mice were coimmunized with various combinations of defined tumor-expressed antigens, telomerase reverse transcriptase (TERT) or TRP-2, and VEGF or VEGFR-2. This study shows that coimmunizing mice against angiogenesis-associated and tumor-expressed antigens can deliver 2 compatible and synergistic cancer treatment modalities via a common treatment, namely immunization.

DOI

10.1182/blood-2002-12-3738

Volume

102

Issue

3

First Page

964

Last Page

971

Disciplines

Medicine and Health Sciences

Link to Full Text
Peer Reviewed

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