[HTML][HTML] Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin

D Sancho, D Mourão-Sá, OP Joffre… - The Journal of …, 2008 - Am Soc Clin Investig
D Sancho, D Mourão-Sá, OP Joffre, O Schulz, NC Rogers, DJ Pennington, JR Carlyle
The Journal of clinical investigation, 2008Am Soc Clin Investig
The mouse CD8α+ DC subset excels at cross-presentation of antigen, which can elicit
robust CTL responses. A receptor allowing specific antigen targeting to this subset and its
equivalent in humans would therefore be useful for the induction of antitumor CTLs. Here,
we have characterized a C-type lectin of the NK cell receptor group that we named DC, NK
lectin group receptor-1 (DNGR-1). DNGR-1 was found to be expressed in mice at high levels
by CD8+ DCs and at low levels by plasmacytoid DCs but not by other hematopoietic cells …
The mouse CD8α+ DC subset excels at cross-presentation of antigen, which can elicit robust CTL responses. A receptor allowing specific antigen targeting to this subset and its equivalent in humans would therefore be useful for the induction of antitumor CTLs. Here, we have characterized a C-type lectin of the NK cell receptor group that we named DC, NK lectin group receptor-1 (DNGR-1). DNGR-1 was found to be expressed in mice at high levels by CD8+ DCs and at low levels by plasmacytoid DCs but not by other hematopoietic cells. Human DNGR-1 was also restricted in expression to a small subset of blood DCs that bear similarities to mouse CD8α+ DCs. The selective expression pattern and observed endocytic activity of DNGR-1 suggested that it could be used for antigen targeting to DCs. Consistent with this notion, antigen epitopes covalently coupled to an antibody specific for mouse DNGR-1 were selectively cross-presented by CD8α+ DCs in vivo and, when given with adjuvants, induced potent CTL responses. When the antigens corresponded to tumor-expressed peptides, treatment with the antibody conjugate and adjuvant could prevent development or mediate eradication of B16 melanoma lung pseudometastases. We conclude that DNGR-1 is a novel, highly specific marker of mouse and human DC subsets that can be exploited for CTL cross-priming and tumor therapy.
The Journal of Clinical Investigation