Enhancing costimulation of T lymphocytes could be harnessed to destroy specific cancer cells but the most effective way to achieve this effect remains unclear. In April Nature Medicine, Zhengmao Ye and colleagues from Pacific Northwest Research Institute, Seattle, show a new antibody gene therapy approach that uses single-chain Fv fragments against the costimulatory T cell receptor 4-1BB.

Ye et al. constructed a vector encoding cell-bound single-chain Fv fragments from the monoclonal anti-4-1BB antibody 1D8, transfected into cells from the K1735 melanoma. They observed that vaccinated mice rejected established wild-type K1735 tumors growing as subcutaneous nodules or in the lung. The transfected cells induced a strong type 1 T-helper cell response, for which CD4⁺ but not CD8⁺ T lymphocytes were necessary and which also involved natural killer cells (Nat Med 2002, 8:343-348).

"Although this approach might be effective for the treatment of human cancers,...