Redirecting Antigens by Engineered Photosynthetic Bacteria and Derived Outer Membrane Vesicles for Enhanced Cancer Immunotherapy

Significant strides have been made in the development of cancer vaccines to combat malignant tumors. However, the natural immunosuppressive environment within tumors, known as the tumor microenvironment (TME), hampers the uptake and presentation of antigens by antigen-presenting cells (APCs) within the tumor itself. This limitation results in inadequate activation of immune responses against cancer. In contrast, immune cells in peritumoral tissue maintain their normal functions. In this context, we present an interesting approach to enhance cancer immunotherapy by utilizing engineered photosynthetic bacteria (PSB) and their outer membrane vesicles (OMV PSB ) to capture and transport antigens to the outer regions of the tumor. We modified PSB with maleimide (PSB-MAL), which, when exposed to near-infrared (NIR) laser-mediated photothermal therapy (PTT), induced extensive cancer cell death and the release of tumor antigens. Subsequently, the NIR-phototactic PSB-MAL transported these tumor antigens to the peripheral regions of the tumor under NIR laser exposure. Even more intriguingly, PSB-MAL-derived OMV PSB -MAL effectively captured and delivered antigens to tumor-draining lymph nodes (TDLNs). This facilitated enhanced antigen presentation by mature and fully functional APCs in the TDLNs. This intricate communication network between PSB-MAL, the OMV PSB -MAL, and APCs promoted the efficient presentation of tumor antigens in the tumor periphery and TDLNs. Consequently, there was a notable increase in the infiltration of cytotoxic T lymphocytes (CTLs) into the tumor, triggering potent antitumor immune responses in both melanoma and breast cancer models. This cascade of events resulted in enhanced suppression of tumor metastasis and recurrence, underscoring the robust efficacy of our approach. Our interesting study, harnessing the potential of bacteria and OMVs to redirect tumor antigens for enhanced cancer immunotherapy, provides a promising path toward the development of personalized cancer vaccination strategies.