VEGF antibodies inhibit growth of NON hodgkins lymphoma

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VEGF antibodies inhibit growth of NON hodgkins lymphoma

Post by Mike Bartolatz » Wed Dec 21, 2005 12:31 pm

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Meeting: 2003 ASCO Annual Meeting Printer Friendly
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Category: Developmental Therapeutics - Molecular Therapeutics
SubCategory: Antiangiogenic or Antimetastatic Agents



Anti-VEGF receptor antibodies inhibit the growth of non-Hodgkin's lymphoma and enhance the effects of chemotherapy or rituximab in lymphoma xenograft mouse models
Abstract No: 841
Citation: Proc Am Soc Clin Oncol 22: page 210, 2003 (abstr 841)
Author(s): E. S. Wang, K. Zhang, J. Teruya-Feldstein, Z. Zhu, D. Hicklin, L. Witte, A. D. Zelenetz, M. A. S. Moore; Memorial Sloan-Kettering Cancer Center, New York, NY; Imclone Systems Inc, New York, NY
Abstract: Vascular endothelial growth factor (VEGF), one of the most potent regulators of angiogenesis, acts through at least two receptors: VEGFR1 (flt1) and VEGFR2 (flk1/ KDR). The precise role of VEGF and its receptors in lymphomagenesis is unclear. We examined B cell non-Hodgkin's lymphoma (NHL) cell lines representative of diffuse large cell and transformed follicular NHL: Hs602, HT, RL, and SKI-DLCL. Immunohistochemistry revealed VEGF in all cells. Flow cytometry demonstrated VEGFR1 and VEGFR2 receptors in all cells. Addition of VEGF or placental growth factor (PlGF), the ligand of VEGFR1, to serum starved lymphoma cells enhanced proliferation in vitro, an effect that was blocked by anti-VEGFR1 and anti-VEGFR2 antibodies. We established lymphoma xenograft models of three human lymphoma cell lines (HT, RL, SKI-DLCL) in immunodeficient mice. To differentiate between VEGFR1 and VEGFR2 mediated autocrine and paracrine pathways, we treated xenografts with neutralizing antibodies against human VEGFR1 (6.12), human VEGFR2/ KDR (IMC-1C11), and murine VEGFR2 receptors (DC101). We found that inhibition of autocrine VEGFR1 and paracrine VEGFR2 pathways, but not autocrine VEGFR2 pathways, led to lymphoma regressions. DC101 treatment markedly reduced tumor growth in all three xenograft models. In addition, combining DC101 treatment with methotrexate or DC101 treatment with anti-CD20 (rituximab) was more effective than single agent therapy alone in reducing lymphoma volumes. Histologic evaluation of xenograft tissue demonstrated decreased blood vessels in DC101 treated tumors as compared to control immunoglobulin or chemotherapy treated tumors. Combination treatment with chemotherapy and DC101 increased tumor apoptosis as compared to single agent or control (immunoglobulin) treated tumors. Conclusions: These data suggest a role for VEGF receptor mediated autocrine and paracrine growth pathways in lymphomagenesis. Combining anti-VEGF receptor antibodies with chemotherapy or immunotherapy may represent a novel therapeutic approach for non-Hodgkin's lymphoma.

Associated Presentation(s):

1. Anti-VEGF receptor antibodies inhibit the growth of non-Hodgkin's lymphoma and enhance the effects of chemotherapy or rituximab in lymphoma xenograft mouse models
Event: 2003 ASCO Annual Meeting
Presenter: Eunice S Wang, MD
Session: Developmental Therapeutics - Molecular
(No presentation available)



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1. Phase I trial of SU011248, a novel tyrosine kinase inhibitor in advanced solid tumors
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2. The role of VEGF expression in response to bevacizumab plus capecitabine in metastatic breast cancer (MBC)
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