Targeting tumor vasculature with novel Listeria-based vaccines directed against CD105

Wood, Laurence; Pan, Zhen-Kun; Guirnalda, Patrick; Tsai, Peter; Seavey, Matthew; Paterson, Yvonne
July 2011
Cancer Immunology, Immunotherapy;Jul2011, Vol. 60 Issue 7, p931
Academic Journal
The FDA approval of bevacizumab (Avastin, Genentech/Roche), a monoclonal antibody raised against human VEGF-A, as second-line therapy for colon and lung carcinoma validated the approach of targeting human tumors with angiogenesis inhibitors. While the VEGF/VEGFR pathway is a viable target for anti-angiogenesis tumor therapy, additional targets involved in tumor neovascularization have been identified. One promising target present specifically on tumor vasculature is endoglin (CD105), a member of the TGF-β receptor complex expressed on vascular endothelium and believed to play a role in angiogenesis. Monoclonal antibody therapy and preventive vaccination against CD105 has met with some success in controlling tumor growth. This report describes the in vivo proof-of-concept studies for two novel therapeutic vaccines, Lm-LLO-CD105A and Lm-LLO-CD105B, directed against CD105 as a strategy to target neovascularization of established tumors. Listeria-based vaccines directed against CD105 lead to therapeutic responses against primary and metastatic tumors in the 4T1-Luc and NT-2 mouse models of breast cancer. In a mouse model for autochthonous Her-2/neu-driven breast cancer, Lm-LLO-CD105A vaccination prevented tumor incidence in 20% of mice by week 58 after birth while all control mice developed tumors by week 40. In comparison with previous Listeria-based vaccines targeting tumor vasculature, Lm-LLO-CD105A and Lm-LLO-CD105B demonstrated equivalent or superior efficacy against two transplantable mouse models of breast cancer. Support is provided for epitope spreading to endogenous tumor antigens and reduction in tumor vascularity after vaccination with Listeria-based CD105 vaccines. Reported here, these CD105 therapeutic vaccines are highly effective in stimulating anti-angiogenesis and anti-tumor immune responses leading to therapeutic efficacy against primary and metastatic breast cancer.


Related Articles

  • Avastin Gets More Time for Review.  // Pharmaceutical Representative;Oct2010, Vol. 40 Issue 10, p10 

    The article accounts on the report issued by the U.S. Food and Drug Administration regarding the extension of the review period for Avastin, a drug used to treat cancer including cancer of the breast, lungs, colon, brain, and kidneys.

  • Medicare to cover expensive cancer treatments.  // PharmacoEconomics & Outcomes News;7/16/2011, Issue 633, p11 

    The article reports on the plan of Medicare to cover Avastin bevacizumab for breast cancer treatment regardless of the decision of the U.S. Food and Drug Administration (FDA) to rescind Avastin approval for such indication in July 2011.

  • Most Doctors Back Avastin Withdrawal.  // Chain Drug Review;2/28/2011, Vol. 33 Issue 4, p93 

    The article reports on the support of fifty-eight percent of physicians in a poll by Sermo, on the move of the Food and Drug Administration (FDA) to pull the breast cancer indication for Avastin from the market.

  • FDA Discusses Listeria Outbreak, Measures Taken. HARPER, ROSEANNE // SN: Supermarket News;10/17/2011, Vol. 59 Issue 42, p36 

    The article discusses the efforts made by Food & Drug Administration (FDA) to control the spread of listeria monocytogenes food poisoning across the U.S. in 2011. The listeria outbreak, caused by cantaloupes, is being considered as the deadliest foodborne illness in U.S. till now. It resulted in...

  • Viral Bacteriophages. Klotter, Jule // Townsend Letter;Jan2008, Issue 294, p25 

    The article reports on the move of the U.S. Food and Drug Administration (FDA) to approve a mixture of six lytic bacteriophages for use on hot dogs, cold cuts, and deli meats in August 2006. It is stated that bacteriophages are viruses that target a specific bacterium to use as a breeding...

  • Cantaloupes Recalled for Listeria.  // Supermarket News Expert Blog;8/2/2012, p2 

    The article focuses on North Carolina supplier Burch Equipment recalling 188,902 cantaloupes tainted with Listeria monocytogenes as to a report of the U.S. Food and Drug Administration (FDA) while infected cantaloupes from Colorado has caused the death of 29 persons and sickness to 139 individuals.

  • NEWSWATCH.  // SN: Supermarket News;1/23/2012, Vol. 60 Issue 4, p36 

    The article offers information on various issues related to supermarket including the new types of fish offered by Wegmans Food Markets, the seizure of the U.S. Food and Drug Administration of all imported shipments of orange juice, and the meeting for the Listeria outbreak in 2011.

  • Bevacizumab in Metastatic Breast Cancer: Ready for Prime Time? Mandock, Katherine; Soefje, Scott A.; Adams, R. // Journal of Hematology Oncology Pharmacy;Dec2011, Vol. 1 Issue 4, p6 

    The article focuses on the U.S. Food and Drug Administration's (FDA) decision to remove bevacizumab's current labeled indication for metastatic breast cancer (MBC). Postapproval trials required with the FDA approval for bevacizumab for treatment did not demonstrate an overall survival (OS)...

  • Fighting Fire with Fire: Rekindling the Bevacizumab Debate. Montero, Alberto J.; Vogel, Charles // New England Journal of Medicine;1/26/2012, Vol. 366 Issue 4, p374 

    The article discusses the controversy concerning the decision of the U.S. Food and Drug Administration (FDA) to revoke bevacizumab approval in 2012. It says that the agency opposed the use of the substance when combined with paclitaxel to treat patients with metastatic breast cancer. According...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics