PMID- 36119832
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220920
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 12
IP  - 8
DP  - 2022
TI  - Clinical feasibility and treatment outcomes with nonselected autologous 
      tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous 
      melanoma.
PG  - 3967-3984
AB  - Nonselected autologous tumor-infiltrating lymphocytes (TILs) may provide 
      advantages over other treatments for solid tumors, including checkpoint 
      inhibitor-refractory melanoma. This retrospective analysis reports a 
      single-center experience of nonselected autologous TILs derived from digested 
      tumors for compassionate use treatment of advanced cutaneous melanoma, including 
      after programmed cell death protein 1 (PD-1) inhibition. Patients with 
      histologically confirmed metastatic cutaneous melanoma and no standard-of-care 
      treatment options underwent tumor resection for TIL product manufacturing. 
      Patients received lymphodepleting chemotherapy with cyclophosphamide for 2 days 
      and fludarabine for 5 days, followed by a single TIL infusion and post-TIL 
      high-dose interleukin (IL)-2. Safety assessments included clinically significant 
      adverse events (AEs). Efficacy assessments included overall response rate (ORR), 
      complete response (CR) rate, disease control rate (DCR), and overall survival. 
      Between October 2011 and August 2019, 21 patients underwent treatment (median 
      follow-up time, 52.2 months from TIL infusion). Among all treated patients, 
      median age was 45 years, median number of disease sites was 4, 100% had M1c or 
      M1d disease, and 90% received prior checkpoint inhibitor. Twelve patients 
      received TILs after prior PD-1 inhibition. The safety profile among all treated 
      patients and the prior PD-1 inhibitor subgroup was generally consistent with 
      lymphodepletion and high-dose IL-2. No treatment-related deaths occurred. Among 
      all patients, the ORR was 67%, CR rate was 19%, and the DCR was 86%, which was 
      consistent with that observed in the prior PD-1 inhibitor subgroup (58%, 8%, and 
      75%, respectively). Median overall survival in all treated patients and the prior 
      PD-1 inhibitor subgroup was 21.3 months. In total, 5 patients (24%) had durable 
      ongoing responses (>30 months post-TIL infusion) at data cutoff, and all patients 
      who achieved CR remained alive and disease free. To further illustrate how TIL 
      therapy may integrate into established treatment paradigms, several case studies 
      of patients treated in this series were included. Overall, these data demonstrate 
      that manufacturing of nonselected autologous TILs from tumor digests is feasible 
      and resulted in high rates of durable response in poor-risk patient populations, 
      which may address significant unmet medical need.
CI  - AJCR Copyright (c) 2022.
FAU - Pillai, Manon
AU  - Pillai M
AD  - Department of Medical Oncology, The Christie, NHS Foundation Trust Manchester, 
      UK.
FAU - Jiang, Yizhou
AU  - Jiang Y
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Lorigan, Paul C
AU  - Lorigan PC
AD  - Department of Medical Oncology, The Christie, NHS Foundation Trust Manchester, 
      UK.
AD  - Division of Cancer Sciences, The University of Manchester Manchester, UK.
FAU - Thistlethwaite, Fiona C
AU  - Thistlethwaite FC
AD  - Department of Medical Oncology, The Christie, NHS Foundation Trust Manchester, 
      UK.
AD  - Division of Cancer Sciences, The University of Manchester Manchester, UK.
FAU - Thomas, Martine
AU  - Thomas M
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Kirillova, Natalia
AU  - Kirillova N
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Bridgeman, John S
AU  - Bridgeman JS
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Kueberuwa, Gray
AU  - Kueberuwa G
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Biswas, Sunetra
AU  - Biswas S
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Velazquez, Peter
AU  - Velazquez P
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Chonzi, David
AU  - Chonzi D
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Guest, Ryan D
AU  - Guest RD
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Roberts, Zachary J
AU  - Roberts ZJ
AD  - Instil Bio, Inc. Dallas, TX, USA.
FAU - Hawkins, Robert E
AU  - Hawkins RE
AD  - Department of Medical Oncology, The Christie, NHS Foundation Trust Manchester, 
      UK.
AD  - Instil Bio, Inc. Dallas, TX, USA.
AD  - Division of Cancer Sciences, The University of Manchester Manchester, UK.
LA  - eng
PT  - Journal Article
DEP - 20220815
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC9441996
OTO - NOTNLM
OT  - PD-1 inhibitor
OT  - T cell
OT  - Tumor-infiltrating lymphocytes
OT  - checkpoint inhibition
OT  - compassionate use
OT  - immunology
OT  - immunotherapy
OT  - interleukin-2
OT  - melanoma
COIS- M. Pillai reports speakers' bureau participation for Bristol Myers Squibb, Ipsen, 
      Pfizer, and Novartis; and travel support from EUSA Pharma and Bristol Myers 
      Squibb. Y. Jiang, P. Velazquez, D. Chonzi, and Z. J. Roberts report employment 
      with and stock or other ownership in Instil Bio, Inc. P. C. Lorigan reports 
      honoraria from Amgen, Merck, Merck Sharp & Dohme (MSD), NeraCare GmbH, Novartis, 
      Oncology Education, Pierre Fabre, and Roche; consultancy or advisory role for 
      Amgen, Bristol Myers Squibb, MSD, Nektar, Novartis, and Pierre Fabre; speakers' 
      bureau participation for Bristol Myers Squibb, MSD, Novartis, and Pierre Fabre; 
      research funding from Bristol Myers Squibb; and travel support from Bristol Myers 
      Squibb and MSD. F. C. Thistlethwaite reports consulting or advisory role for 
      Achilles, Bayer, Bristol Myers Squibb, Evelo Therapeutics, GSK, T-knife, and 
      Zelluna Immunotherapy; research funding from Novartis; and serves as the 
      coordinating or local physician investigator for AbbVie, Achilles Ltd, 
      Adaptimmune, Agalimmune, AstraZeneca, AVEO, Bristol Myers Squibb, Chugai 
      Pharmaceutical Co., CytomX, Daiichi Sankyo, GenMab, GSK, Immunocore, Incyte, 
      Janssen, Kymab Ltd, Millennium Pharmaceuticals/Takeda, Novartis, Pfizer, Roche, 
      and Synthon. M. Thomas reports employment with Cellular Therapeutics, Ltd, 
      Immetacyte, Ltd, and Instil Bio, Inc. N. Kirillova reports former employment with 
      and stock or other ownership in Immetacyte, Inc; and stock or other ownership in 
      Instil Bio, Inc. J. S. Bridgeman reports employment with Instil Bio, Inc; stock 
      or other ownership in Immetacyte and Instil Bio, Inc; and patents, royalties, or 
      other intellectual property from Instil Bio, Inc. G. Kueberuwa reports employment 
      with, stock or other ownership in, and patents, royalties or other intellectual 
      property from Instil Bio, Inc. S. Biswas reports employment with Instil Bio, Inc; 
      stock or other ownership in Instil Bio, Inc. and Kite, a Gilead Company; and 
      patents, royalties, or other intellectual property from City of Hope. R. D. Guest 
      reports employment with, stock or other ownership in, and patents, royalties, or 
      other intellectual property from Instil Bio, Inc; and leadership role at 
      Immetacyte, Inc. R. E. Hawkins reports employment with and stock or other 
      ownership in Instil Bio, Inc; consultancy or advisory role for Anaveon AG and 
      NovalGen, Ltd; and nonexecutive director for and stock or other ownership in 
      Bivictrix Plc.
EDAT- 2022/09/20 06:00
MHDA- 2022/09/20 06:01
PMCR- 2022/08/15
CRDT- 2022/09/19 04:33
PHST- 2022/06/15 00:00 [received]
PHST- 2022/07/14 00:00 [accepted]
PHST- 2022/09/19 04:33 [entrez]
PHST- 2022/09/20 06:00 [pubmed]
PHST- 2022/09/20 06:01 [medline]
PHST- 2022/08/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2022 Aug 15;12(8):3967-3984. eCollection 2022.