Adoptive T cell
immunotherapy, such as
chimeric antigen receptor (CAR) T cell therapy, has proven to be highly efficient in the treatment of
hematologic malignancies. However, it is challenged by complicated ex vivo engineering, systemic side effects, and low expression of
tumor-specific
antigen, especially in solid
tumors. In this paper, we present a "recognition-then-activation" strategy, which first assists naïve T cells to recognize and adhere to
cancer cells and then activates the accumulated T cell in situ to specifically kill
cancer cells. In this way, we could unleash the antitumor power of the T cell without complicated and time-consuming cell engineering. To this end, circular bispecific aptamers (cb-aptamers), a class of chemically cyclized aptamers with improved stability and molecular recognition ability which can simultaneously bind to two different types of cells, were first constructed to form artificial intercellular recognition between naïve T cells and
tumor cells. After T cell accumulation in the
tumor mediated by cb-aptamers, T cells in the
tumor site were subsequently activated in situvia commercial CD3/CD28 T cell activator beads to induce
tumor-specific killing. Furthermore, by simply choosing different anticancer aptamers, the application of this "recognition-then-activation" strategy can be expanded for targeted treatment of various types of
cancer. This may represent a simple T cell
immunotherapy that is useful for the treatment of multiple
cancers.