Abstract
“Cold” tumor with insufficient CD8+ T cell infiltration and the up-regulated programmed cell death protein 1 (PD-1) on activated T cell surface are the two main obstacles in preventing effective cancer immunotherapy. Herein, we firstly leverage pH-responsive micelles (pRML) with photosensitizer 2-(1-hexyloxyethyl)−2-devinyl pyropheophorbide-a (HPPH) encapsulation (pRML/HPPH) via photodynamic-immunotherapy to pre-activate CD8+ T cells. Subsequently, pH-responsive polymersomes (pRPS) with interleukin-2 (IL-2) encapsulation and anti PD-1 fragment (Fab’) decoration on surface (Fab-pRPS/IL-2) are fabricated to target the pre-activated T cells with immune checkpoint blockade and T cell proliferation. From in vivo study results, the sequential cancer immunotherapy of pRML/HPPH and Fab-pRPS/IL-2 reveals high antitumor activity and abscopal effect in B16F10 tumor-bearing mice, as well as displays more effective antitumor activity than co-injection method. This work provides an approach to enhancing immune response via sequential therapy to target the pre-activated T cells with immune checkpoint blockade.
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