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Journal ArticleDOI

Hybrid antibodies can target sites for attack by T cells

Uwe D. Staerz, +2 more
- 18 Apr 1985 - 
- Vol. 314, Iss: 6012, pp 628-631
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TLDR
It is shown that heteroconjugates of monoclonal antibodies (referred to hereafter as hybrid antibodies), in which one of the component binding sites is anti-T-cell receptor and the other component binding site is directed against any chosen target antigen, can focus T cells to act at the targeted site.
Abstract
It would be advantageous in the case of certain diseases to be able to focus a strong T-cell response at a chosen target, for example, in treating cancer or infections that have escaped the normal host response. At present, it seems inconceivable that we could use antigen-specific lines or clones of effector T cells for this purpose because of complications due to the major histocompatibility restriction of T-cell specificity and the problem of rejection of transplanted effector cells. Here we describe a novel technology which combines the power of T lymphocytes in eliminating unwanted cells and causing beneficial inflammatory reactions with the great advantages of monoclonal antibodies (their specificity and availability). We show that heteroconjugates of monoclonal antibodies (referred to hereafter as hybrid antibodies), in which one of the component binding sites is anti-T-cell receptor and the other component binding site is directed against any chosen target antigen, can focus T cells to act at the targeted site. Monoclonal antibodies directed against the T-cell receptor, such as the anti-allotype used here, are mitogenic for resting T cells and can be used to induce effector T cells carrying the T-cell receptor determinant which can then be directed against the target by a hybrid antibody.

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Citations
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Dual variable domain immunoglobulins and uses thereof

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References
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Journal ArticleDOI

Protein thiolation and reversible protein-protein conjugation. N-Succinimidyl 3-(2-pyridyldithio)propionate, a new heterobifunctional reagent

TL;DR: A heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio)propionate, was synthesized and its N-hydroxysuccinimide ester group reacts with amino groups and the 2- pyridyl disulphide structure reacts with aliphatic thiols, resulting in a new thiolation procedure for proteins.
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Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells.

TL;DR: The specificity of these antibodies and their ability to stimulate cloned helper T cells in the absence of antigen and antigen-presenting cells strongly suggest that these antibodies are directed against antigen and/or Ia recognition sites on the T cell.
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Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression.

TL;DR: The same correlation with respect to isotype expression was found, indicating that hybridoma antibodies reflect normal antibody responses and suggesting H-2-linked control of this expression.
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Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones.

TL;DR: Results imply that anticlonotypic antibody functions in a fashion analogous to antigen and further support the notion that the T3-Ti molecular complex represents the antigen receptor on human T lymphocytes.
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