ApoVax-SVN as a Novel Vaccine for Cancer Immunotherapy

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$328,300.00
Award Year:
2007
Program:
STTR
Phase:
Phase I
Contract:
1R41CA121665-01A2
Award Id:
85390
Agency Tracking Number:
CA121665
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
APOIMMUNE, INC, 1044 E CHESTNUT ST, LOUISVILLE, KY, 40204
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
140646345
Principal Investigator:
HAVAL SHIRWAN
(502) 852-2066
HAVAL.SHIRWAN@LOUISVILLE.EDU
Business Contact:
() -
kmacleod@apoimmune.com
Research Institute:
UNIVERSITY OF LOUISVILLE

UNIVERSITY OF LOUISVILLE
OFFICE OF GRANTS MANAGEMENT
LOUISVILLE, KY, 40292 3098

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): The main objective of this proposal is to develop a novel cancer vaccine, ApoVax-SVN(tm) based on the use of a proprietary costimulatory chimeric ligand, 4-1BBL, designed to specifically deliver survivin, a tumor associ ated antigen (TAA) to professional antigen-presenting cells (APCs) and activate them for the generation of an effective anti-tumor immune response with therapeutic efficacy for cancer immunotherapy. Therapeutic vaccines represent an attractive treatment mo dality for the management of cancer, primarily due to their specificity and ability to induce long lasting immunological memory that may prevent against recurrences. However, their therapeutic potential remains to be realized partially due to the complex n ature of interactions taking place between the immune system and cancer cells in the course of tumor progression. These interactions are primarily regulated by two opposing forces; immune mechanisms that target the tumor for destruction and tumor-mediated counter-mechanisms that enable the tumor to evade the immune system. As such, to be effective tumor vaccines must be capable of generating a potent anti-tumor immune response as well as overcoming immune evasive mechanisms for a therapeutic effect. Various cancer vaccine approaches based on the use of TAAs have been developed and shown effective in preclinical models. However, the therapeutic efficacy of these vaccines has been limited in clinical trial settings. Although the reasons for their clinical inef ficacy remain unknown, the lack of a strong adjuvant effect, ineffective delivery of TAAs to professional APCs, and/or the presence of significant immunoinhibitory immune evasion mechanisms may contribute to this effect. To overcome some of these difficult ies, a novel technology designated as ProtEx(tm) has recently been developed by the Principle Investigator of this application. ProtEx(tm) involves the generation of chimeric immunological ligands with a modified form of core streptavidin, modification of the cell membrane with biotin, and decoration with chimeric proteins. There are three distinct advantages to this technology. First, chimeric ligands exist as tetramers and higher structures, and as such effectively crosslink their receptors on immune cell s for potent signal transduction. Second, chimeric proteins can be displayed singly or in a combination on the surface of any biotinylated cell at desired levels in a rapid (lt 2 hrs), efficient (100% of the targeted cells), and durable (t1/2= days to week s) manner without compromising the function of the protein or the cell. Third, chimeric proteins can be conjugated to biotinylated molecules of interest via streptavidin/biotin interaction and used as vehicles to deliver such molecules to cells of interest expressing receptors for the chimeric proteins. The Principle Investigator of this application recently developed a novel, proprietary potential cancer vaccine approach based on the use of 4-1BBL chimeric molecule conjugated to biotinylated TAA antigens. In preliminary studies, this novel vaccine showed potent stimulatory activity on the innate as well as adaptive arms of the immune system and inhibitory activity on T regulatory cells implicated in tumor growth. More importantly, since the last submission of this grant we have demonstrated that immunization with SA-4-1BBL plus a synthetic peptide representing the CD8+ T cell epitope of E7 was effective in eradicating established tumors in a cervical cancer animal model. Therefore, the objectives of this pro posal are to test and determine in vivo conditions required for protective as well as therapeutic effects of ApoVax-SVN(tm) vaccine using a B cell lymphoma transplantable model expressing survivin as a TAA. Proof-of-principle confirmation in experimental c ancer models will pave the way for testing this novel concept in human clinical trials. Immune system-based treatment of cancer represents an alternative the

* information listed above is at the time of submission.

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