We have used serological approaches to define a variety of cell surface antigens on human and murine tumors, to guide the biochemical characterization of these antigens and to monitor approaches to augmenting their immunogenicity in whole cell vaccine trials. Two of these antigens are now available in purified form, the Meth A antigen and the AH antigen (GD2). The Meth A antigen is an individually distinct murine tumor antigen identified on the chemically induced Meth A sarcoma by sera from immunized syngeneic BALB/c mice. It is a protein (molecular weight approximately 75K) which is closely related or identical to the Meth A transplantation antigen. The AH antigen was originally defined by sera from melanoma patient AH. It has been detected in high titer on the cell surface of human and murine melanomas. It has also been detected on some other tissues of neural crest origin, generally in lower titer. The AH antigen has recently been identified as the ganglioside GD2. We propose to augment the immunogenicity of purified forms of these 2 very different antigens using 4 general approaches to vaccine construction. We will determine which vaccines result in the best serological response against GD2 and the Meth A antigen. We will also determine which vaccines result in the strongest cutaneous delayed hypersentsitivity reactions to GD2 and Meth A antigens and the best protection from, and treatment of, the corresponding tumors (Meth A sarcoma and the recently established murine melanoma JB-RH) in syngeneic mice. The 4 general approaches and the specific vaccines to be tested in each approach are listed below: 1. Meth A antigens and GD2 injected with adjuvants or immunogenic carriers such as complete Freunds adjuvant, muramyl dipeptides (MDP), detoxified endotoxin plus BCG cell wall skeletons, formyl peptide chemoattractants, salmonella and liposomes; 2. Meth A antigens and GD2 covalently attached to MDP, BSA or formyl peptide chemoattractants; 3. Meth A antigen fixed and aggregated with glutaraldehyde; 4. The optimal approaches described obove in conjuction with antisuppressor cell treatments such as low dose cyclophosphamide, cimetidine indocin, isoprenosine and NPT 15392.
