Abstract
Recently, the emergence of immunotherapy has revolutionized traditional tumour treatment. However, effective treatments for patients exhibiting αPD-1 resistance are still lacking. In our study, a combination of cytosine–phosphate–guanine oligodeoxynucleotides (CpG-ODNs), anti-OX40 and cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) injection in situ systematically generated a robust antitumour immune response in TC1 and B16 cells, which are αPD-1-resistant malignancies. More precisely, this method activates both adaptive and innate immunity. Additionally, in situ vaccination with CpG/αOX40/cGAMP fully activates the production of cytokines. However, the combination of αPD-1 does not improve the efficacy of triple therapy, prompting further questions. Collectively, the combination of CpG/αOX40/cGAMP causes the regression of various αPD-1-resistant tumours through the full mobilization of innate and adaptive immunity. In addition, we explored the therapeutic effect of triple therapy on the αPD-1-sensitive cell line CT26. The results showed that triple therapy could significantly enhance the therapeutic effect of αPD-1, and some mice even achieved complete tumour regression after the combined application of αPD-1 and triple treatment.
Highlights
The incidence and mortality rates of cancer are increasing gradually and are primary factors threatening human health
The most common immunotherapy is PD-1/PD-L1 immune checkpoint inhibitors, which have been administered to many patients with cancer and have achieved a high response rate and lasting remission, significantly improving the survival rate of patients with recurrent or refractory Hodgkin's lymphoma [2,3,4], non-small cell lung cancer (NSCLC) [5,6,7], melanoma [8,9,10], etc., showing broad application prospects
Mice bearing TC1/B16 tumours were treated with αPD-1 (100 μg/mouse) 3 times, but no difference in tumour volume was observed between the treatment group and the PBS group (Fig. 2a–b)
Summary
The incidence and mortality rates of cancer are increasing gradually and are primary factors threatening human health. The traditional treatment methods for cancer include surgery, radiotherapy, chemotherapy and targeted therapy; each of these treatment methods has limitations, so the recurrence and metastasis of tumours remains a challenge, leading to a poor prognosis and low long-term survival rate in patients with advanced tumours. Tumour immunotherapy is mainly divided into four categories according to the method: non-specific immune modulators, adoptive cell therapy, immune checkpoint inhibitors and tumour vaccines. The most common immunotherapy is PD-1/PD-L1 immune checkpoint inhibitors, which have been administered to many patients with cancer and have achieved a high response rate and lasting remission, significantly improving the survival rate of patients with recurrent or refractory Hodgkin's lymphoma [2,3,4], non-small cell lung cancer (NSCLC) [5,6,7], melanoma [8,9,10], etc., showing broad application prospects. An effective treatment must be developed for αPD-1-resistant patients
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