Description

In vivo Proof-of-Principle

Raising efficient immune response to target antigens is one of the rate limiting steps towards generation of effective vaccines. Generation of adaptive immune response relies on presentation of antigens by specialised antigen presenting cells. Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. However, there are a number of sub-types of DCs, some of which are highly efficient at cross-presentation of the exogenous antigen.

The CD8+ DCs in mice (but not in humans) have been known to be highly efficient at cross-presentation of antigens and activation of T cell response. Dr Reis e Sousa’s laboratory have identified a C-type lectin receptor - CLEC9A (also known as DNGR-1) - that is selectively expressed in murine CD8+ DCs and, crucially, in a subset of human DCs that are highly efficient at cross-presentation. Proof-of-principle evidence in vivo demonstrates that targeted delivery of antigens using anti-CLEC9A antibodies elicits potent T-cell response that is translated in anti-cancer efficacy in both prophylactic and therapeutic setting. 

A number of other C-type lectins, such as DEC205 and DCSIGN, have been identified in the past as potential receptors for antibody targeted vaccines. However, these targets are expressed in a number of other cell types as well as on the target APCs. In contrast, expression of CLEC9A is highly restricted to the subset DCs – allowing specific delivery of antigens to a small fraction of DCs that are efficient at crosspresentation.

Download the PDF of CLEC9A: A Novel Dendritic Cell Antibody Target

For more information please contact

Dr Raj Mehta

+44 (0) 20 3469 6300 .(JavaScript must be enabled to view this email address)