Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo (Nature Medicine, 11:130-137, February 2005)

報告日期: 2005/09/23
報告時間: 16:00/16:50
報告學生: 顏孟畿
講評老師: 林以行
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Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.

 

Speaker 顏孟畿                       Time:4:00PM 2005/9/23

commentator:林以行老師                Place602教室

 

Abstract:

Dendritic cells (DCs) are one kind of the antigen presenting cells with a unique capacity to stimulate naive T cells. DCs can generate immune response against tumor through ex vivo induced by tumor antigen. However, the outcomes of recent DC vaccine trials suggest the refinement of DC vaccine design. In order to enhance DC vaccine efficacy, the authors have engineered a potent, drug-inducible CD40 (iCD40) receptor that contains a membrane-localized cytoplasmic domain of CD40 fused to drug-binding domains. iCD40 receptor can respond to a lipid-permeable, high-affinity dimmer drug, AP20187. With this modifications, iCD40 receptor not only trigger downstream NF-κB signal pathway but also prolong activation of iCD40-expressing DCs in vivo, especially inducing more CD8+ T-cell responses. Besides, iCD40-mediated DC activation had better efficiency than full-length, endogenous CD40 in vitro. In addition, iCD40 DC vaccine had significantly higher efficiency than wide type under the same vaccination condition in animal models, either. Because of the longer lifespan and stronger immune responses of iCD40-expresing DCs, it was suggested that in vivo iCD40 stimulation of DC-based vaccines can greatly enhance antitumor potency which might be a promising therapeutic approach in immune-compromised patients.

 

Reference:

1. Hanks et al. Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell vaccines in vivo. Nat. Med. 11: 130-137 (2005).

2. Berzofsky et al. Progress on new vaccine strategies for the immunotherapy and prevention of cancer. J. Clin. Invest. 113:1515–1525 (2004).

3. Nestle et al. Debdritic cells: on the move from bench to bedside. Nat. Med. 7: 761-765 (2001).