Antiangiogenic and antitumoral therapy delivered by a dual-expression L. monocyto

Award Information
Agency:
Department of Health and Human Services
Branch:
N/A
Amount:
$210,739.00
Award Year:
2009
Program:
SBIR
Phase:
Phase I
Contract:
1R43CA137915-01A1
Agency Tracking Number:
CA137915
Solicitation Year:
2009
Solicitation Topic Code:
N/A
Solicitation Number:
PHS2009-2
Small Business Information
ADVAXIS, INC.
675 Highway one, North Brunswick, NJ, 08902
Hubzone Owned:
Y
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
140232815
Principal Investigator
 PAULO MACIAG
 (609) 356-8307
 PAULO.MACIAG@BMS.COM
Business Contact
Phone: (732) 545-1590
Email: wallecha@advaxis.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): Breast cancer is the second most common type of cancer in females, causing over 40,000 deaths in the United States annually. Recently, cancer vaccines have arisen as a potential therapy and several target antigens have been identified in Breast cancer, including Her2/neu antigen. The goal of cancer vaccines is to generate effector T cells that are able to infiltrate and kill the tumor cells. We propose to generate a single recombinant Listeria monocytogenes capable of targeting cancer cells and tumor vasculature by concomitant expression of Her2 and HMW-MAA, which is expressed in pericytes and plays a role in tumor angiogenesis. To address this challenge, a dual-expression Lm platform is created by expressing Her2 from the chromosome and HMW-MAA from a plasmid. To enhance immunogenicity, both antigens are fused to the virulence factor listeriolysin-O and immune responses and therapeutic efficacy of the dual-expression system will be evaluated, including analysis of tumor-infiltrating lymphocytes and tumor vasculature. Delivery of an anti-angiogenic antigen simultaneously with a tumor-associated antigen will likely have a synergistic effect in impacting tumor growth by targeting blood vessels, which might enhance effector T cell infiltration in the tumor and improve the vaccine therapeutic efficacy, besides creating a flexible platform for future use. PUBLIC HEALTH RELEVANCE: Breast cancer is a major health problem in female population, causing the death of over 40,000 American men annually. In this SBIR Phase I project, Advaxis Inc. will construct a novel, clinically suitable recombinant Listeria monocytogenes capable of targeting Her2 expressing breast cancer cells and tumor vasculature concomitantly, which will be tested in a mouse tumor model.

* information listed above is at the time of submission.

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