局部晚期错配修复能力正常结直肠癌患者新辅助用博替西单抗加巴替西单抗的治疗效果模式。
Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.
发表日期：2023 Sep 21
作者：
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T H Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P Rocca, Allyson J Ocean, Elizabeta C Popa, Daniel H Hunt, Nikhil P Uppal, Kelly A Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A Shah, Erika Hissong
来源：
ONCOGENE
摘要：
在没有远处转移的局部晚期癌症患者中，新辅助治疗提供了评估新药物的平台。对于失配修复能力正常/微卫星稳定（pMMR/MSS）结直肠癌，免疫治疗显示出有限的疗效。在本文中，我们报道了两例pMMR/MSS结直肠癌患者，在新辅助治疗时观察到与botensilimab（BOT）和balstilimab（BAL）相关的杰出疗效。BOT是一种经Fc增强的下一代抗CTLA-4抗体，BAL是一种抗PD-1抗体。在这一设置中，观察到的快速免疫反应的组织学模式（“内外”（浆膜至粘膜）肿瘤退缩）尚未被描述过。通过空间生物学分析（RareCyte Inc.），我们揭示了BOT的作用机制，即一种新型的先天性-适应性免疫活化剂。这些观察结果对于使用新辅助免疫疗法并潜在地减少患者化疗的临床试验设计具有重要影响。© 2023. The Author(s).
In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed ("inside-out" (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.© 2023. The Author(s).