USA flag logo/image

An Official Website of the United States Government

Therapeutic Vaccine for HIV/HPV-associated Oropharyngeal and Tonsillar…

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2011 / SBIR
Agency Tracking Number:
R43DE021973
Solicitation Year:
2011
Solicitation Topic Code:
NIDCR
Solicitation Number:
PA10-050
Small Business Information
ETUBICS CORPORATION
9715 FREMONT AVE N SEATTLE, WA 98103-3140
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2011
Title: Therapeutic Vaccine for HIV/HPV-associated Oropharyngeal and Tonsillar Malignanci
Agency: HHS
Contract: 1R43DE021973-01
Award Amount: $163,405.00
 

Abstract:

DESCRIPTION (provided by applicant): The objective of this project is to develop a therapeutic strategy for H V-associated malignancy based on the role of HPV in the pathogenesis. HPV related cancers express the E6/E7 oncoproteins of HPV that are ideal targets for immune inducing vaccines. We will develop a vaccine based upon a novel adenovirus serotype-S vector (Ads) platform with unique and additional deletions of the viral DNA polymerase and the pre- terminal protein in the early gene 2b (E2b) region (Ads [E1-, E2b-]). In studies employing HIV antigens, we reported that the new Ad5 [E1-, E2b-]-HlV vector vaccine was superior to a current Ads [E1-]-H V vector vaccine (containing deletion in the early gene 1 (E1) region) when used to induce CMI responses ina multiple immunization regimen. Significant antigen specific CMI responses were induced in mice and monkeys despite the presence of pre-existing AdS immunity. We will construct and produce an AdS [E1-, E2b-] vector vaccine that contains the HPV oncoproteins E6/E7 with non-oncogenic function. This new recombinant adenovirus will induce immune responses by expressing the modified HPV-E6/E7 antigens after direct transfection of antigen presenting cells. We will evaluate this in combination with a toll-like receptor agonist (TLRa) designed to enhance immune responses induced by the vaccine. Our pre-clinical data indicate that the AdS [E1-, E2b-] vec*or induces robust CMI responses against tumor associated antigen [fAA), even in the presence of pre- existing AdS immunity. In a murine cancer model employing the carcinoembryonic antigen (CEA) gene insert, tl.g -CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with i new AdS [E1-, E2b-l- GEA were compared to those observed with a currentgeneration Ads tE1-l-CEA. These AdS vectors were tested in a clinically relevant AdS immune setting. We observed that AdS immune mice immunized multiple times with AdS [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in AdS immune mice immunized multiple times with a current generation AdS tE1-l-CEA. Ads immune mice bearing CEA expressing tumors that were treated with AdS [E1-, E2b-J-CEA had an increased anti-tumor response as compared to AdS [E1-I-CEAtreated mice. These results demonstrate that AdS [E1-, Ezb-l-CEA can induce CMI immune responses that result in tumor growth inhibition despite the presence of pre-existing AdS immunity. We have also utilized the Ads [E1-, Ezb-] vector platform expressingthe TAA HER2lneu as a breast cancer immunotherapeutic agent. Ads [E1-, E2b-l-HERZlneu induced potent CMI against HER2/neu and significantly inhibited progression of established tumors in Ad5 immune mice. These data demonstrate that in vivo delivery of Ad5[E1-, E2b-] vectors expressing TM can induce anti-TAA immunity and inhibit progression of tumors in AdS immune animals. PUBLIC HEALTH RELEVANCE: In this study, we will develop a new adenoviral based drug (AdS [E1-, E2b-I-HPV-E6/7) to treat HtV+ patients with HPv-associated oropharyngeal and tonsillar ,ncers. The treatment platform is needed to overcome pre-existing AdS immunity that has prevented the widespread use of this type of technology.

Principal Investigator:

Frank R. Jones
206-838-5110
frank@etubics.com

Business Contact:

Carol R. Jones
206-838-5110
cj@etubics.com
Small Business Information at Submission:

ETUBICS CORPORATION
410 W HARRISON ST, STE 100 SEATTLE, WA 98119-

EIN/Tax ID: 120003520
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No