Document 0153
 DOCN  M95A0153
 TI    Genetic modification of T cell clones to improve the safety and efficacy
       of adoptive T cell therapy.
 DT    9510
 AU    Greenberg PD; Nelson B; Gilbert M; Sing A; Yee C; Jensen M; Riddell SR;
       Department of Medicine, University of Washington, Seattle 98195,; USA.
 SO    Ciba Found Symp. 1994;187:212-23; discussion 224-8. Unique Identifier :
       AIDSLINE MED/95317145
 AB    Our laboratory has developed methods to isolate human antigen-specific
       cytolytic CD8+ T cell clones and to expand such clones in vitro to
       numbers sufficient for T cell therapy of human diseases. Studies in
       immunocompromised bone marrow transplant patients at high risk for
       disease associated with cytomegalovirus have demonstrated that
       administration of more than 10(9) CD8+ T cell clones is safe and can
       effectively reconstitute a deficient human immune response. Our
       laboratory is applying this strategy of adoptive therapy to the
       treatment of human cancer, starting with the subset of patients with
       Hodgkin's disease who show expression of proteins encoded by the
       Epstein-Barr virus in their malignant Reed-Sternberg cells. The
       development of efficient systems such as retroviral vectors for the
       introduction of genes into primary cells has made it possible to
       consider overcoming some of the limitations of the effector T cells that
       normally mediate response to an antigen. Our laboratory is attempting to
       modify T cell clones by the introduction of genes before transfer as a
       means to improve the safety and/or efficacy of T cell therapy.
 DE    Antigens, Viral/IMMUNOLOGY  Bone Marrow Transplantation/IMMUNOLOGY
       Clone Cells  Cytomegalovirus Infections/PREVENTION & CONTROL/*THERAPY
       CD8-Positive T-Lymphocytes/IMMUNOLOGY  Human  Immunocompromised
       Host/*IMMUNOLOGY  Immunotherapy, Adoptive/*ADVERSE EFFECTS  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Suppressor-Effector/*PHYSIOLOGY  JOURNAL ARTICLE

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