Therapeutic DNA Vaccination Against Colorectal Cancer via MYB Targeting

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The oncoprotein and transcription factor MYB is overexpressed in colorectal cancer and critical to proliferation and tumor cell survival. In a study reported in Clinical & Translational Immunology, Cross and colleagues developed a DNA vaccine to generate an MYB-specific immune response on the hypothesis that MYB peptides are aberrantly presented on the surface of colorectal cancer cells.

The fusion vaccine consisted of a full-length MYB cDNA joined to two CD4 epitopes from tetanus toxoid, with multiple inactivating mutations being inserted into the oncogene sequence. Vaccination was tested against tumors initiated by the MYB-expressing cancer cell lines CT26 in BALB/c mice and MC38 in C57BL/6 mice. Low-dose cyclophosphamide was used to overcome T-regulatory cell immune suppression and anti–PD-1 (programmed cell death protein 1) antibodies were used to block T-cell exhaustion.

No antitumor effect was observed in either mouse model with cyclophosphamide alone; anti–PD-1 antibody produced a slight delay in tumor growth in MC38-bearing mice and a greater delay in CT26-bearing mice. Therapeutic vaccination resulted in a protective effect when the MC38 tumor burden was low and was found to induce tumor-specific cell killing and increased protection when MC38 and CT26 tumor burdens were higher and when the vaccine was used in combination with an anti–PD-1 antibody or cyclophosphamide. ■

Cross RS, et al: Clin Transl Immunol 4:e30, 2015.




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