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Targeting of human immunodeficiency virus-infected cells by CD8+ T
lymphocytes armed with universal T-cell receptors
MR Roberts, L Qin, D Zhang, DH Smith, AC Tran, TJ Dull, JE Groopman, DJ Capon, RA Byrn and MH Finer
Cell Genesys Inc, Foster City, CA.
We have developed an immunotherapeutic approach with potential application
in the treatment of viral and malignant disease. We show that primary CD8+
T cells isolated from peripheral blood can be genetically modified by
retroviral transduction to express high levels of universal (major
histocompatibility complex-unrestricted) chimeric T- cell receptors
specific for human immunodeficiency virus (HIV) antigens. Two classes of
HIV-specific URs in which the antigen-binding domain is comprised of either
CD4 or a single-chain antibody are capable of activating a number of T-cell
effector functions in response to target cells, including cytolysis, in a
highly sensitive and specific manner. Importantly, we have addressed a
number of issues which, although particularly relevant to the clinical
application of this approach in the treatment of HIV infection, may also
impact on the potential of UR immunotherapy for other disease targets. The
UR immunotherapeutic system is particularly suited for evaluation in the
clinical setting.
Volume 84,
Issue 9,
pp. 2878-2889,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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