Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

14
The T-Body Approach: Towards Cancer Immuno-Gene Therapy
Jehonathan H. Pinthus and Zelig Eshhar
14.1
Background
Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
The T-body approach employs T cells redirected with antibody specificity using chimeric
receptors (CRs). In this chapter we use the term T-bodies to define T cells bearing
surface CRs. In functional terms, the CR combines antibody specificity in the
form of Fv (variable region fragment) linked to a T cell stimulatory molecule. Primarily,
we developed the T-body approach in order to endow T cells with predefined antibody
specificity in order to study some physicochemical parameters involved in T
cell activation (for review, see [1]). In the first design of the CR, we tookadvantage of
the similarity in structure and genetic organization between the T cell receptor
(TCR) and the antibody molecules, and replaced the variable (V) region of the TCR a
and b chains with the antibody VH and VL [2]. Using the V region of antihapten antibodies
we demonstrated that T cell hybridoma expressing such chimeric TCR genes
could recognize antigen in an MHC-unrestricted manner, and could undergo activation
for IL-2 production and target cell killing in a non-MHC-dependent manner [1].
Quite readily,we and others have appreciated that T-bodies with antitumor specificity
hold promise for cancer immunotherapy (for reviews, see [3, 4]). The idea behind
this assumption was to combine the availability of monoclonal antibodies (mAbs) towards
tumor-associated antigens with the efficacy of tumor penetration and rejection
of T cells. Using this combination we expected to overcome the inefficiency of antibodies
in rejecting solid tumors, on the one hand, and difficulties in obtaining tumor-specific
T cells, on the other.
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