Nanomaterial-based delivery vehicles for therapeutic cancer vaccine development

Nanomaterial-based delivery vehicles such as lipid-based,polymer-based,inorganics-based,and bio-inspired vehicles often carry distinct and attractive advantages in the development of therapeutic cancer vaccines.Based on various delivery vehicles,specifically designed nanomaterials-based vaccines are highly advantageous in boosting therapeutic and prophylactic antitumor immunities.Specifically,therapeutic vaccines featuring unique properties have made major contributions to the enhancement of antigen immunogenicity,encapsulation efficiency,biocompatibility,and stability,as well as promoting antigen cross-presentation and specific CD8^(+)T cell responses.However,for clinical applications,tumor-associated antigen-derived vaccines could be an obstacle,involving immune tolerance and deficiency of tumor specificities,in achieving maximum therapeutic indices.However,when using bioinformatics predictions with emerging innovations of in silico tools,neoantigen-based therapeutic vaccines might become potent personalized vaccines for tumor treatments.In this review,we summarize the development of preclinical therapeutic cancer vaccines and the advancements of nanomaterial-based delivery vehicles for cancer immunotherapies,which provide the basis for a personalized vaccine delivery platform.Moreover,we review the existing challenges and future perspectives of nanomaterial-based personalized vaccines for novel tumor immunotherapies.

Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.