DNA vaccination places tumors in double jeopardy

The ER resident chaperone protein calreticulin plays a surprising variety of roles in cell regulation, some of which make it particularly appealing for antitumor vaccination. First, this protein can be cleaved in vivo to form the potent antiangiostatic factor vasostatin. In addition, when expressed in antigen presenting cells, calreticulin interacts with the peptide processing machinery to facilitate loading of associated peptides with the Class I MHC complex. Building on recent evidence that presentation of tumor-associated peptides through calreticulin can promote tumoricidal immune responses, Cheng et al. have engineered a fusion gene encoding a known viral tumor antigen, linked directly to the chaperone. They report here that mice exposed subdermally to this DNA construct enjoy seemingly complete resistance to tumor cells that express the viral antigen. Conversely, a simple mixture of the viral sequence and the calreticulin sequence has minimal effect, suggesting that calreticulin-mediated immune antigen presentation is crucial. Mice that are treated with calreticulin DNA but that lack CD8 T cells are susceptible to tumor growth, but even they appear to benefit somewhat from the effects of vasostatin, since their tumors show significantly less vascular development. It remains to be seen if this form of combined antiangiogenesis and antitumor immunity can be applied more generally by fusing calreticulin to other tumor antigens.

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