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Article: Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer

TitleAllogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer
Authors
KeywordsAllogeneic γδ T cells
New expansion formula
Cell therapy
Liver cancer
Lung cancer
Issue Date2021
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html
Citation
Cellular & Molecular Immunology, 2021, v. 18, p. 427-439 How to Cite?
AbstractVγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.
DescriptionHybrid open access
Persistent Identifierhttp://hdl.handle.net/10722/299733
ISSN
2020 Impact Factor: 11.53
2020 SCImago Journal Rankings: 2.500
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorXu, Y-
dc.contributor.authorXiang, Z-
dc.contributor.authorAlnaggar, M-
dc.contributor.authorKouakanou, L-
dc.contributor.authorLi, J-
dc.contributor.authorHe, J-
dc.contributor.authorYANG, J-
dc.contributor.authorHu, Y-
dc.contributor.authorChen, Y-
dc.contributor.authorLin, L-
dc.contributor.authorHao, J-
dc.contributor.authorLi, J-
dc.contributor.authorChen, J-
dc.contributor.authorLi, M-
dc.contributor.authorWu, Q-
dc.contributor.authorPeters, C-
dc.contributor.authorZhou, Q-
dc.contributor.authorLi, J-
dc.contributor.authorLiang, Y-
dc.contributor.authorWang, X-
dc.contributor.authorHan, B-
dc.contributor.authorMa, M-
dc.contributor.authorKabelitz, D-
dc.contributor.authorXu, K-
dc.contributor.authorTu, W-
dc.contributor.authorWu, Y-
dc.contributor.authorYin, Z-
dc.date.accessioned2021-05-26T03:28:18Z-
dc.date.available2021-05-26T03:28:18Z-
dc.date.issued2021-
dc.identifier.citationCellular & Molecular Immunology, 2021, v. 18, p. 427-439-
dc.identifier.issn1672-7681-
dc.identifier.urihttp://hdl.handle.net/10722/299733-
dc.descriptionHybrid open access-
dc.description.abstractVγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/cmi/index.html-
dc.relation.ispartofCellular & Molecular Immunology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAllogeneic γδ T cells-
dc.subjectNew expansion formula-
dc.subjectCell therapy-
dc.subjectLiver cancer-
dc.subjectLung cancer-
dc.titleAllogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer-
dc.typeArticle-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.authorityTu, W=rp00416-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41423-020-0515-7-
dc.identifier.pmid32939032-
dc.identifier.pmcidPMC8027668-
dc.identifier.scopuseid_2-s2.0-85091178584-
dc.identifier.hkuros322484-
dc.identifier.volume18-
dc.identifier.spage427-
dc.identifier.epage439-
dc.identifier.isiWOS:000570036300001-
dc.publisher.placeChina-

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