Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy

There is now clear clinical evidence that adoptive cellular immunotherapy can eradicate hematologic malignancy and cure otherwise lethal viral infections. With this knowledge comes the challenge of improving the effectiveness and safety of the approach and of simplifying the methodologies required whilst still meeting appropriate federal regulatory guidelines. This review provides an overview of the current status of cellular immunotherapies and addresses how they may be implemented and the future directions they are likely to take. In Section I, Dr. Brenner with Drs. Rossig and Sili reviews the clinical experience to date with adoptive transfer of viral antigen-specific T cells for the successful treatment of Epstein-Barr virus-associated malignancies as well as viral infectious diseases. Genetic modification of the T cell receptor of the infused cells to potentiate such T cells as well as modifications to improve safety of the infusions are described. In Section II, Dr. Young describes the hematopoietic lineages of human dendritic cells and some of their immunotherapeutic applications. The critical importance of dendritic cells to T cell immunity and the capacity to generate dendritic cells in large numbers has spawned enormous interest in the use of these specialized leukocytes to manipulate cellular immunity. Successful cytokine-driven differentiation of dendritic cells reveal two types, myeloid- and plasmacytoid or lymphoid-related dendritic cells. The effects of maturation on phenotype and function of the dendritic cells and their use as immune adjuvants in dendritic cell vaccines to elicit antitumor and antiviral immunity are reviewed. In Section III, Professor Goulmy illustrates some current and future approaches towards tumor-specific cellular therapy of hematopoietic malignancy. Minor histocompatibility antigen (mHag) disparities between HLA-matched bone marrow donor and recipient can induce allo-responses that may participate in post bone marrow transplantation (BMT) graft-versus-leukemia (GVL) reactivities. A lack of such allo-reactivity may result in relapse of leukemia after BMT. In these patients, adoptive immunotherapy with cytotoxic T cells (CTLs) specific for hematopoietic system-restricted mHags may be used as an extension of current efforts using immunotherapy with donor lymphocyte infusions. Adoptive immunotherapy with CTLs specific for the hematopoietic system-restricted mHags, however, offers the prospect of greater and more predictable effectiveness in the absence of graft-versus-host disease.