Engineering Immune Effector Molecules and Cells for Immunotherapy of Cancer and Autoimmunity

Antibody and protein engineering approaches are used in our laboratory to develop new cancer immunotherapy strategies which combine the advantage of the well-established tumor targeting capabilities of high affinity recombinant fragments of antibodies with the known efficient, specific, and potent killing ability and unique specificity of CD8 T lymphocytes directed against highly antigenic MHC/peptide complexes or other effector functions.

Two approaches have been developed by our research team. First, is a new class of recombinant chimerical molecules created by the genetic fusion of scFv antibody fragments, specific for tumor cell surface antigens, to monomeric single-chain HLA-A2 complexes containing immunodominant tumor or viral-specific peptides. Second, are unique recombinant antibodies that mimic the fine specificity of the T cell receptor and recognize tumor and viral specific peptide-MHC complexes.

The molecular feature of these molecules/approaches and their in vitro and in vivo activities will be described. The future development of these approaches as new modalities to immunotherapy, bridging antibody and T lymphocyte attack on cancer cells, will be discussed in the context of their development path to clinical trials humans.

The use of these novel molecules to study basic questions of tolerance will be described as well demonstrating the bridge between basic and translational immunological research.