Editors' ChoiceCancer

A captive peptide for T cell activation

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Science Translational Medicine  27 Jul 2016:
Vol. 8, Issue 349, pp. 349ec121
DOI: 10.1126/scitranslmed.aah4508

Cancer immunotherapy boosts the immune system’s ability to seek out and, ultimately, destroy cancer cells. One of the most effective ways of mediating an antitumor immune response is through the generation of cytotoxic T cells. These potent immune cells directly kill their target cells in addition to secreting cytokines such as interferon-γ, which aid in tumor rejection. Because the tumor microenvironment actively suppresses the differentiation of cytotoxic T cells, immunotherapy is required to provoke an adequate anticancer response.

In a recent study, Choi and colleagues demonstrated the ability of dendritic cell therapy to induce cytotoxic T cell–mediated killing of melanoma cells in mice. The authors engineered protein cage nanoparticles made of the bacterial protein, encapsulin. The resultant encapsulin nanocompartments were 30 nm in diameter, which is an ideal size for navigating the lymphatic system. Furthermore, they were capable of carrying diverse cargos, including the antigenic peptide, OT-1, used in these experiments.

To establish proof of principle, the authors devised a model system in which OT-1, an 8-amino acid residue of the protein ovalbumin, was used in conjunction with a melanoma cell line genetically engineered to express ovalbumin. In mouse experiments, encapsulin cage nanoparticles delivered OT-1 to dendritic cells, which subsequently presented the antigen to naïve T cells. Treatment induced OT-1 specific T cell differentiation into cytotoxic T cells in the spleen and increased interferon-γ production. Subcutaneous melanoma tumor growth was markedly hindered when immunotherapy was used prophylactically. Results were more modest when the vaccination was administered 10 days after tumor inoculation, although the authors speculate that a booster injection would improve outcomes.

This study underscores the potential of encapsulin cage nanoparticles in enabling the dendritic cell–mediated activation of cytotoxic T cells for cancer cell killing. Utility is anticipated to be highest when used at early stages of tumor generation, when it is easiest for T cells to infiltrate the tumor. Future work is needed to extend results in this model ovalbumin system to a human tumor model and to evaluate the utility and timing of booster administration. Ultimate translation will depend on the identification of antigenic peptide sequences specific to the type of cancer being treated.

B. Choi et al., Effective delivery of antigen–encapsulin nanoparticle fusions to dendritic cells leads to antigen-specific cytotoxic T cell activation and tumor rejection. ACS Nano 10.1021/acsnano.5b08084 (2016). [Abstract]

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