AI Article Synopsis
- The study focused on developing costimulatory molecules to enhance T cell responses in cancer treatment using a virus-modified tumor vaccine.
- Researchers created bispecific antibodies that target both T cell receptors (CD3 and CD28) and a viral protein from Newcastle Disease Virus (NDV).
- These antibodies effectively redirected T cells to kill NDV-infected tumor cells, leading to strong T cell activation and proliferation, as well as the release of immune-signaling molecules.
Article Abstract
The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.
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| http://dx.doi.org/10.1016/j.vaccine.2004.10.031 | DOI Listing |
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