This CATBRM proposal will carry out clinical trials with recombinant tumor vaccines. We will utilize the patients' specific humoral and cellular immune response to the recombinant protein as the intermediate endpoint to optimize the therapeutic regimen. In general, these studies will be done in patients with low tumor burdens (no evidence of disease with high risk of recurrence) since they are the most likely group to respond and the likely target population for clinical application. The Tumor Vaccine CATBRM is composed of a Clinical Program; Humoral Immunity Program; Cellular Immunity Program; Genetics/Cell Culture Core Laboratory; and a collaborating investigator (J. Schlom). The initial protocol involves the use of a recombinant vaccinia-carcinoembryonic antigen (rV-CEA) vaccine to be tested in low tumor burden colon cancer patients. Group I patients will receive an initial immunization (10-8 pfu by intradermal route) with a repeat dose (booster) 8 weeks later. Group II patients will receive the same dose and schedule but also receive cyclophosphamide 3 days prior to each immunization for immune modulation. Patients will be monitored for specific immune response to CEA by four assay systems for antibody to CEA (with appropriate controls and specificity studies) and four assays of cellular immunity to CEA (lymphoblastic transformation, IL-2 release, IL-6 release and cytolytic T cell assays to autologous CEA expressing target cells). Patients will also be monitored for delayed hypersensitivity skin test reactivity to purified preparations of CEA and NCA (non-specific cross-reacting antigen) as well as for side effects or toxicity. The statistical design utilizes a novel multiple stage procedure to test the hypothesis that the substantive immune response rate is 50% or more. The objective of the study is to develop a regimen which induces a """"""""substantive"""""""" immune response to CEA in the majority of recipients with an emphasis on cellular immunity. The Tumor Vaccine CATBRM is designed to analyze prospective recombinant vaccines utilizing an efficient strategy to determine the feasibility of any particular vaccine to induce the immune response which underlies the rationale for its use. These trials may involve variables of dose administered and/or schedule or in the case of the rV-CEA, fixed dose with the variable of booster immunization or cytoxan immunomodulation.
| Conry, R M; Allen, K O; Lee, S et al. (2000) Human autoantibodies to carcinoembryonic antigen (CEA) induced by a vaccinia-CEA vaccine. Clin Cancer Res 6:34-41 |
| Lee, S W; Li, H; Strong, T V et al. (2000) Development of a polynucleotide vaccine from melanoma antigen recognized by T cells-1 and recombinant protein from melanoma antigen recognized by T cells-1 for melanoma vaccine clinical trials. J Immunother 23:379-86 |
| Rodenburg, C M; Mernaugh, R; Bilbao, G et al. (1998) Production of a single chain anti-CEA antibody from the hybridoma cell line T84.66 using a modified colony-lift selection procedure to detect antigen-positive ScFv bacterial clones. Hybridoma 17:1-8 |
