Abstract
It is well established that natural killer (NK) cells can be used as an alternative candidate of T cells for adoptive cell therapy (ACT) due to its high killing capacity, off-the-shelf utility, and low toxicity. Though NK cells provide rapid and potent immune effects, they still suffer from insufficient infiltration and tumor immunosuppression environment, which result in unsatisfactory therapeutic efficiency. Herein, a highly stable CD16/PD-L1 bi-specific aptamer (defined as CP-bi-apt) with high affinity and selectivity was introduced to overcome these obstacles. This CP-bi-apt can mediate a significant antitumor immunity by recruiting CD16-positive NK cells to directly contact with PD-L1 high-expressed tumor cells. In addition, the induced up-regulation of PD-L1 on tumor cells can inevitably occur as an adaptive response to most of the immunotherapeutic strategies. The prepared CP-bi-apt can be further used as an immune checkpoint inhibitor to specifically bind to PD-L1, thus reducing the negative impact of PD-L1 over-expression on the therapeutic efficacy. Furthermore, this CP-bi-apt-based immunotherapy is simple, highly efficient, and has low side effects, showing a promising potential for clinical translation.
Highlights
Adoptive cell therapy (ACT) has become one of the most flexible and potent cancer treatments that can elicit partial and even complete regression of various malignancies.[1]
In summary, a novel CD16/PD-L1 bi-specific aptamer named CP-biapt was developed for cancer immunotherapy that integrates the functions of immune checkpoint blockade and the recruitment of natural killer (NK) cells to tumor site without any additional procedures
The prepared CP-bi-apt can form a completely closed structure with the help of T4 DNA ligase, which can significantly enhance its stability. This aptamer can mediate a significant antitumor immunity by recruiting CD16-positive NK cells to directly contact with PD-L1 high-expressed tumor cells
Summary
Adoptive cell therapy (ACT) has become one of the most flexible and potent cancer treatments that can elicit partial and even complete regression of various malignancies.[1]. The insufficient infiltration and the low abundance of NK cells in solid tumors can only lead to limited therapeutic success.[12,13]. To address this problem, great efforts have been implemented to endow NK cells with the functions of tumor homing and infiltration. Great efforts have been implemented to endow NK cells with the functions of tumor homing and infiltration To this aim, NK cells are usually modified by genetic engineering or chemical methods, which are relatively tedious and hard to reproduce and may cause new safety concerns
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