Development of a Novel CEA Expressing Ad5 [E1-, E2b-] Vector for Treatment

DESCRIPTION (provided by applicant): The objective of this project is to continue to develop an adenoviral vector vaccine against CEA that is effective in stimulating cell-mediated immune responses in subjects previously immune to Adenovirus. The Ad-CEA vaccine endpoint is to treat patients with CEA bearing cancers. CEA is a tumor associated protein that has been reported to be useful as a vaccine treatmen target. Evidence indicates that a broad cell-mediate immune (CMl) response is needed to treat certain CEA bearing tumors. Adenovirus vector vaccines induce CMI responses and have emerged as a leading candidate to be used as a treatment vaccine delivery platform. First generation Adenovirus vaccines have proven less effective than anticipated and adverse reactions are in question. Furthermore pre-existing Adenovirus immunity of most humans causes decreased effectiveness. To address these issues, we have developed an advanced Adenovirus based vector that is devoid of early genes E1, E3,and E2b. These E2b deleted vectors, with deletions in the polymerase and preterminal protein genes, have an expanded cloning capacity and greatly reduced expression of viral late genes as compared to First Generation Adenoviral vectors. The reduced expression of multiple Adenoviral genes has been demonstrated to be advantageous for vaccine development for reasons such as reduced antigenic competition, greater longevity of expression which provides increased immunologic stimulus and reduced adverse effects. Such advantage are important in the presence of pre-existing Adenoviral immunity, and provide the E2b Adenoviral vectors with stealth like attributes. The Company has exclusive license for the new Adenoviral vector system and the E.C7 cell line that supports vector production. The proposed studies are designed to construct and further test the effectiveness of a CEA vaccine based on this new Adenoviral vector platform which will carry the CEA gene. Our Phase I studies tested this new vaccine for the potential to induce CEA memory CMI response as a prime and re-immunization (boost) potential in Ad-na ve and Ad-immune mice. Based upon our successful results observed in the Phase I studies, we propose to conduct human clinical Phase l/ll trials in our current project proposal. PUBLIC HEALTH RELEVANCE: This study will further develop pre-clinical information and lead to clinical trials of a new drug (Ads [E1-, E2b-]-CEA) to treat cancers which have carcinoembryonic antigen on their surface. The drug is needed to induce a greater immune response against certain cancers.