150
G. Yang and Y. Huang
Fig. 6.7 Characterization of CD28 aptamers. a Aptamer sequences. b Computer secondary
structure prediction of the two aptamers against CD28 [174]
signal. On the contrary, CD28Apt7 monomer has no activity. However, the dimers of
the two aptamers provide artificial co-stimulatory signals. It has been proved in vivo
that the activated CD28 aptamer enhances the anti-tumor immune response induced
by idiotypic vaccine in mouse lymphoma model, thus improving the overall survival
rate to a great extent. It is worth noting that the function of CD28Apt2 monomer
(antagonist) is opposite to that of dimer (agonist). At present, no other therapeutic
agent can achieve this dual function except adaptation in vitro.
In 2016, Fernando Pastor group [181] identified aptamers of multidrug resistanceassociated protein 1 (MRP1) for targeting chemotherapy-resistant tumors. Furthermore, a MRP1-CD28 aptamer dimer was designed, which can bind to tumorous
tumors expressing MRP1 and transmit CD28 co-stimulatory signals to tumor
infiltrating lymphocytes. Bispecific aptamers can enhance the co-stimulation of
chemotherapy-resistant tumors. Melanoma-bearing mice treated with MRP1-CD28
aptamer dimer showed growth inhibition, which proved the improvement of mouse
survival. Aptamers can form bispecific heterodimers, but antibodies are difficult to
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