Immunotherapy of Malignant Tumors Using Antisense Anti-IGF-I Approach: Case of Glioblastoma

The review article describes the criteria established for methodology of antisense anti IGF-I therapy of malignant tumors, particularly of glioblastoma. The cancer patients, after classical therapy of surgery, radiotherapy and chemotherapy, have undergone the injection of genetically modified autologous malignant cells—transfected by IGF-I antisense/triple helix expression vectors. For all cancer patients supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients, the following common immune criteria for “anti IGF-I” strategy were admitted: 1) characteristics of cell “vaccines”—absence of IGF-I and expression of MHC-I in cloned transfected cells;2) the peripheral blood lymphocytes, PBL cells, removed after every of two successive vaccinations, demonstrate an increasing level of CD8+ and CD8+28+ molecules (with a switch from CD8+11b+ to CD8+11b-).

Preliminary Exploration of the Clinical Features and Immunological Correlation between TIGIT and Esophageal Squamous Cell Carcinoma

Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.

Immunostimulatory CKb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer

Immunosuppression tumor microenvironment(TME)seriously impedes anti-tumor immune response,resulting in poor immunotherapy effect of cancer.This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells,resulting in high CKb11 secretion from tumor cells,successfully activating immune cells and increasing cytokine secretion to reshape the TME,and ultimately delaying tumor progression.The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.It can cause high expression of IFN-γ,which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells.Therefore,combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense,leading to a collaborative anti-tumor outcome.Thus,utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites,thereby reshaping immunosuppressive TME for cancer treatment,has great potential as an immunogene therapy in clinical applications.

Non-viral vector mediated CKb11 with folic acid modification regulates macrophage polarization and DC maturation to elicit immune response against cancer

The immunosuppressive tumor microenvironment(TME)of cancer strongly hinders the anti-tumor immune responses,thereby resulting in disappointing responses to immunotherapy.Chemoattractive and promotive traits of chemokines exerted on leukocytes have garnered interest in improving the efficiency of immunotherapy by increasing the infiltration of immune cells in the TME.In this study,a folic acid(FA)-modified gene delivery system based on the self-assembly of DOTAP,MPEG-PCL-MPEG,and FA-PEG-PCL-PEG-FA,namely F-PPPD,was developed to deliver plasmids encoding the immunostimulating chemokine CKb11.The delivery of plasmid CKb11(pCKb11)by F-PPPD nanoparticles resulted in the high secretion of CKb11 from tumor cells,which successfully activated T cells,suppressed the M2 polarization of macrophages,promoted the maturation of dendritic cells(DCs),facilitated the infiltration of natural killer(NK)cells and inhibited the infiltration of immunosuppressive cells in tumor tissues.Administration of F-PPPD/pCKb11 also significantly suppressed the cancer progression.Our study demonstrated a nanotechnology-enabled delivery of pCKb11,that remodeled the immunosuppressive TME,for cancer treatment.