UHで開発された技術が、リンパ腫の治療を前進させる可能性(Technology Developed at UH Could Advance Treatment of Lymphoma)


CAR T細胞免疫療法の成功を決定する貴重な時間を節約する発見 Discovery Saves Valuable Time, Determines Success of CAR T-Cell Immunotherapy

2022-08-24 ヒューストン大学(UH)

キメラ抗原受容体(CAR) T細胞療法に反応しそうな患者を判定する方法を発見しました。この方法は、この免疫療法に最も反応しやすいリンパ腫の治療において貴重な時間を節約することができます。CAR T細胞療法は、すべての患者さんに効果があるわけではなく、中には深刻な副作用を経験する患者さんもいるため、これは貴重な知見。


多次元単一細胞解析により、臨床抗腫瘍T細胞応答におけるCD2-CD58相互作用の役割が明らかになった Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses

Gabrielle Romain, Paolo Strati, Ali Rezvan, Mohsen Fathi, Irfan N. Bandey, Jay R.T. Adolacion, Darren S. Heeke, Ivan Liadi, Mario L. Marques-Piubelli, Luisa M. Solis Soto, Ankit Mahendra, Francisco Vega, Laurence J.N. Cooper, Harjeet Singh, Mike Mattie, Adrian Bot, Sattva Neelapu, and Navin Varadarajan
Journal of Clinical Investigation    Published July 26, 2022


The in vivo persistence of adoptively transferred T cells is predictive of anti-tumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific CAR T cells that comprise the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on Timelapse Imaging Microscopy In Nanowell Grids (TIMING) that integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We identified that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed elevated CD58 expression on pre-treatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T-cell tumor cell interactions in identifying optimal antitumor responses.