Generation of whole tumor cell vaccine for on-demand manipulation of immune responses against cancer under near-infrared laser irradiation.
Jiaqi MengYanlin LvWeier BaoZihui MengShuang WangYuanbin WuShuping LiZhouguang JiaoZhi-Yuan TianGuanghui MaWei WeiPublished in: Nature communications (2023)
The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.
Keyphrases
- immune response
- dendritic cells
- photodynamic therapy
- heat shock
- drug delivery
- cancer therapy
- toll like receptor
- radiation induced
- high throughput
- cell therapy
- squamous cell carcinoma
- climate change
- stem cells
- adipose tissue
- signaling pathway
- preterm infants
- fluorescence imaging
- mass spectrometry
- young adults
- high speed
- heat stress
- metabolic syndrome
- mesenchymal stem cells
- case report
- preterm birth
- anti inflammatory
- lymph node metastasis
- childhood cancer