| 公告主旨 |
[演講] 7/14 顧正崙 老師 主講：Return of the Anti-IFN-γ: From Disease Mechanism to Therapeutic Approach |
| 公告內容 |
臺大基蛋所Medical Genetics & Genomics Monthly Seminar演講邀請
[講題]：Return of the Anti-IFN-γ: From Disease Mechanism to Therapeutic Approach
[講者]：顧正崙 特聘教授（長庚大學 分子免疫中心）
CV:https://www.mc.ntu.edu.tw/medgenpro/News.action?q_type=-1&q_itemCode=10394
[時間]：2025/7/14 （星期一） 上午11：20-12：10
[Hybrid Meeting]:
*地點: 醫學院基醫大樓202講堂
*Webex: https://ntumc.webex.com/ntumc-tc/j.php?MTID=m1580d80b620c776de3eb12b9c165523c
[摘要]
Anti–interferon-γ autoantibodies （AIGAs） are key drivers of adult-onset immunodeficiency in Southeast Asia, predisposing individuals to infections such as Talaromyces marneffei and nontuberculous mycobacteria. Using single-cell capture, we cloned 19 monoclonal AIGAs and identified three distinct epitopes on IFN-γ. While all clones exhibited high-affinity binding （KD < 10⁻⁹ M）, only a subset neutralized IFN-γ–STAT1 signaling. Mechanistic studies revealed that epitope group I antibodies block IFN-γ binding to IFN-γR1, whereas group II and III antibodies interfere with IFN-γR1–R2 dimerization even after receptor engagement. Notably, group III antibodies also mediated antibody-dependent cellular cytotoxicity （ADCC）, potentially depleting IFN-γ–responsive cells. To therapeutically eliminate these pathogenic antibodies, we developed IFN-γ chimeric autoantibody receptor （CAAR） T cells using an engineered, receptor-nonbinding IFN-γ variant. These CAAR T cells selectively targeted autoreactive B cells from patients, reduced circulating AIGAs in a mouse model, and avoided off-target and Fc-mediated toxicity. This precision approach offers a promising strategy for restoring IFN-γ immunity in affected patients. Meanwhile, due to their potent and specific cytokine-blocking activity, AIGAs are also being repurposed as therapeutic agents for IFN-γ–driven autoimmune diseases such as vitiligo, where IFN-γ contributes to melanocyte destruction. Our work highlights both the pathogenic mechanisms of AIGAs and innovative therapeutic strategies that transform disease insights into clinical applications.
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