Dendritic cell-based immunotherapy for colon cancer using an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope from tumor-associated antigen 90K

Abstract

Tumor-associated antigen 90K is implicated in cell-cell and cell-extracellular matrix adhesion through its interaction with galectin-3 and integrin-b1 and is highly expressed in malignant tissues, making it a novel target for the development of new immunotherapies. We investigated a potential immunotherapy treatment for colon cancer using 90K-specific cytotoxic T lymphocytes induced by autologous dendritic cells and pulsed with 90K peptides. We selected three peptides (90K 351 , 90K 5 and 90K 523 ) that bind to HLA-A*0201 molecules on the basis of their binding affinity, as determined by a peptide-T2 binding assay. Dendritic cells pulsed with 90K peptides resulted in the efficient generation of mature dendritic cells and exhibited enhanced T-cell stimulation and polarization of naive T cells toward Th1. Dendritic cells pulsed with 90K peptides generated potent cytotoxic T-lymphocytes that lysed T2 cells loaded with each 90K peptide, and 90K1 /HLA-A2 1 colon cancer cell lines, including HCT116 and SW480, in a dose-dependent and HLA-A*0201-restricted manner. No killing was observed in 90K 1 /HLA-A2 2 DLD1 or 90K 2 /HLA-A2 2 K562 cells. Therefore, we believe that cytotoxic T-lymphocytes stimulated by 90K peptide-pulsed dendritic cells naturally recognize the 90K peptide presented by colon cancer cells in the context of HLA-A2, and kill 90K-positive tumor cells. Dendritic cells pulsed with 90K peptides led to the induction of granzyme B and perforin positive CD8 1 T cells against HCT116 and SW480 cells, but not DLD1 cells. In conclusion, 90K-specific cytotoxic T lymphocytes, generated by stimulating T cells with 90K peptide-pulsed dendritic cells, could be useful effector cells for the immunotherapy treatment of colon cancer.

Overexpression of long non-coding RNA00355 enhances proliferation, chemotaxis, and metastasis in colon cancer via promoting GTF2B-mediated ITGA2

“…Previously conducted studies have suggested many tumor-associated antigens (TAA) such as 90 K [35] , 4D10 [36] and GTF2B [23] may serve as targets for colon cancer therapy [37] . Moreover, the relationship between GTF2B, lncRNA LINC00355 and ITGA2 was verified in our study, which showed that overexpression of lncRNA LINC00355 was conducive to promoting the binding of GTF2B to ITGA2.…”

A tumor-to-lymph procedure navigated versatile gel system for combinatorial therapy against tumor recurrence and metastasis

“…Recent studies ( 7 – 9 ) have shown that enhancing patients’ antitumor immunity is the best approach to prevent and control tumor metastasis. Cancer immunotherapeutic approaches, such as cancer vaccines ( 10 , 11 ), checkpoint blockade therapies ( 12 , 13 ), and cell-based therapies [such as dendritic cell (DC)–based T cell adoptive transfer] ( 14 – 16 ), have shown promise. Thus, introducing immunotherapeutic strategies with DDS appears to be a feasible approach to counter metastasis and tumor recurrence.…”

Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1

“…LGALS3BP encodes the galectin-3-binding protein (Gal-3BP), which was originally reported by several groups in attempts to search for proteins secreted by cancer cells (9, 10). Extending from its discovery, the role of Gal-3BP has been widely studied in the field of cancer research (11–19). Since Gal-3BP has a scavenger receptor cysteine-rich (SRCR) domain, which is found in innate immunity-related proteins, the role of Gal-3BP has also been extensively studied in relation to immune reactions (20, 21).…”