Adoptive Immunotherapy of Human Diseases with Antigen-Specific T-Cell Clones

Abstract

Cellular adoptive immunotherapy refers to the transfer of effector cells of the immune system to treat infectious or malignant diseases. Our laboratory has been investigating the use of adoptive immunotherapy with antigen-specific T-cell clones to prevent cytomegalovirus (CMV) infection in allogeneic bone marrow transplant (BMT) recipients; augment immune responses to human immunodeficiency virus (HIV) in HIV-seropositive individuals; and to induce a graft-versus-leukemia (GVL) response in allogeneic BMT recipients. In each of these settings the rationale for developing adoptive immunotherapy is based on clear evidence that deficiencies of antigen-specific T cells are responsible for disease progression. Functional studies of effector activity and genetic markers have been used to demonstrate that adoptively transferred T-cell clones can persist and function in the host and migrate appropriately to sites of disease. It is anticipated that additional studies will define disease settings in which T-cell therapy can be beneficial and further elucidate the requirements for effective immunotherapy in humans.