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)
T細胞と腫瘍細胞の動的相互作用について研究した。その結果、癌細胞上のリガンド分子(CD58)とT細胞上のタンパク質(CD2)の関係が明らかになり、これらの分子が互いに作用してCD2を活性化し、癌細胞に対する殺傷力を高めることが分かった。
研究チームは、T細胞と腫瘍細胞間の何千もの相互作用を調べることで、CD2とCD58の間の重要な相互作用を特定しました。
<関連情報>
- https://uh.edu/news-events/stories/2022-news-articles/august-2022/08242022-lymphoma-t-cell-immunotherapy-varadarjan.php
- https://www.jci.org/articles/view/159402
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
DOI:10.1172/JCI159402
Abstract
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.
