Industrializing engineered autologous T cells as medicines for solid tumours

被引:17
作者
Britten, Cedrik M. [1 ,3 ]
Shalabi, Aiman [2 ]
Hoos, Axel [2 ]
机构
[1] GlaxoSmithkline, Oncol R&D, Stevenage, Herts, England
[2] GlaxoSmithkline, Oncol R&D, Philadelphia, PA 19112 USA
[3] Immat Biotechnol, Munich, Germany
关键词
CHIMERIC ANTIGEN RECEPTOR; INFILTRATING LYMPHOCYTE THERAPY; TERM-FOLLOW-UP; LISOCABTAGENE MARALEUCEL; METASTATIC MELANOMA; TRANSCEND NHL; CANCER-IMMUNOTHERAPY; COMPLETE RESPONSES; PATIENTS PTS; SAFETY;
D O I
10.1038/s41573-021-00175-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Cell therapy is one of the fastest growing areas in the pharmaceutical industry, with considerable therapeutic potential. However, substantial challenges regarding the utility of these therapies will need to be addressed before they can become mainstream medicines with applicability similar to that of small molecules or monoclonal antibodies. Engineered T cells have achieved success in the treatment of blood cancers, with four chimeric antigen receptor (CAR)-T cell therapies now approved for the treatment of B cell malignancies based on their unprecedented efficacy in clinical trials. However, similar results have not yet been achieved in the treatment of the much larger patient population with solid tumours. For cell therapies to become mainstream medicines, they may need to offer transformational clinical effects for patients and be applicable in disease settings that remain unaddressed by simpler approaches. This Perspective provides an industry perspective on the progress achieved by engineered T cell therapies to date and the opportunities and current barriers for accessing broader patient populations, and discusses the solutions and new development strategies required to fully industrialize the therapeutic potential of engineered T cells as medicines.
引用
收藏
页码:476 / 488
页数:13
相关论文
共 173 条
[1]   Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study [J].
Abramson, Jeremy S. ;
Palomba, M. Lia ;
Gordon, Leo I. ;
Lunning, Matthew A. ;
Wang, Michael ;
Arnason, Jon ;
Mehta, Amitkumar ;
Purev, Enkhtsetseg ;
Maloney, David G. ;
Andreadis, Charalambos ;
Sehgal, Alison ;
Solomon, Scott R. ;
Ghosh, Nilanjan ;
Albertson, Tina M. ;
Garcia, Jacob ;
Kostic, Ana ;
Mallaney, Mary ;
Ogasawara, Ken ;
Newhall, Kathryn ;
Kim, Yeonhee ;
Li, Daniel ;
Siddiqi, Tanya .
LANCET, 2020, 396 (10254) :839-852
[2]  
Abramson JS, 2019, J CLIN ONCOL, V37
[3]   Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL. [J].
Abramson, Jeremy S. ;
Gordon, Leo I. ;
Palomba, Maria Lia ;
Lunning, Matthew Alexander ;
Arnason, Jon E. ;
Forero-Torres, Andres ;
Wang, Michael ;
Maloney, David G. ;
Sehgal, Alison ;
Andreadis, Charalambos ;
Purev, Enkhtsetseg ;
Solomon, Scott R. ;
Ghosh, Nilanjan ;
Albertson, Tina M. ;
Xie, Benhuai ;
Garcia, Jacob ;
Siddiqi, Tanya .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)
[4]   CAR T-cell Integration of Multiple Input signals Allows for Precise Targeting of Cancer [J].
Achkova, Daniela ;
Pule, Martin .
CANCER DISCOVERY, 2018, 8 (08) :918-920
[5]   Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: Safety and preliminary efficacy in combination with anti-PD-1 agent. [J].
Adusumilli, Prasad S. ;
Zauderer, Marjorie Glass ;
Rusch, Valerie W. ;
O'Cearbhaill, Roisin ;
Zhu, Amy ;
Ngai, Daniel ;
McGee, Erin ;
Chintala, Navin ;
Messinger, John ;
Cheema, Waseem ;
Halton, Elizabeth ;
Diamonte, Claudia ;
Pineda, John ;
Vincent, Alain ;
Modi, Shanu ;
Solomon, Stephen Barnett ;
Jones, David Randolph ;
Brentjens, Renier J. ;
Riviere, Isabelle ;
Sadelain, Michel .
JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (15)
[6]  
Aftab B.T., 2020, ADV CELL GENE THER, V3, DOI 10.1002/acg2.v3.310.1002/acg2.86
[7]   Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma [J].
Al-Hadidi, Samer A. ;
Chuang, Hubert H. ;
Miranda, Roberto N. ;
Lee, Hun Ju .
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA, 2021, 21 (02) :E105-E111
[8]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[9]   Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen [J].
Andersen, Rikke ;
Donia, Marco ;
Ellebaek, Eva ;
Borch, Troels Holz ;
Kongsted, Per ;
Iversen, Trine Zeeberg ;
Holmich, Lisbet Rosenkrantz ;
Hendel, Helle Westergren ;
Met, Ozcan ;
Andersen, Mads Hald ;
Straten, Per Thor ;
Svane, Inge Marie .
CLINICAL CANCER RESEARCH, 2016, 22 (15) :3734-3745
[10]   Enhanced activity of second-generation MAGE-A4 SPEAR T-cells through co-expression of a CD8α homodimer [J].
Anderson, Victoria E. ;
Weber, Anika M. ;
Wiedermann, Guy E. ;
Pachnio, Anette ;
Dauleh, Sumaya ;
Ahmed, Tina ;
Docta, Roslin Y. ;
Quattrini, Adriano ;
Pope, George ;
Quinn, Laura ;
Ashton, Thomas M. ;
Tunbridge, Helen M. ;
Sanderson, Joseph P. ;
Gerry, Andrew B. .
CANCER RESEARCH, 2019, 79 (13)