PMID- 35149146
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220706
IS  - 1873-1899 (Electronic)
IS  - 0734-9750 (Linking)
VI  - 58
DP  - 2022 Sep
TI  - Better by design: What to expect from novel CAR-engineered cell therapies?
PG  - 107917
LID - S0734-9750(22)00013-1 [pii]
LID - 10.1016/j.biotechadv.2022.107917 [doi]
AB  - Chimeric antigen receptor (CAR) technology, and CAR-T cells in particular, have 
      emerged as a new and powerful tool in cancer immunotherapy since demonstrating 
      efficacy against several hematological malignancies. However, despite encouraging 
      clinical results of CAR-T cell therapy products, a significant proportion of 
      patients do not achieve satisfactory responses, or relapse. In addition, CAR-T 
      cell applications to solid tumors is still limited due to the tumor 
      microenvironment and lack of specifically targetable tumor antigens. All current 
      products on the market, as well as most investigational CAR-T cell therapies, are 
      autologous, using the patient's own peripheral blood mononuclear cells as 
      starting material to manufacture a patient-specific batch. Alternative cell 
      sources are, therefore, under investigation (e.g. allogeneic cells from an at 
      least partially human leukocyte antigen (HLA)-matched healthy donor, universal 
      "third-party" cells from a non-HLA-matched donor, cord blood-derived cells, 
      immortalized cell lines or cells differentiated from induced pluripotent stem 
      cells). However, genetic modifications of CAR-engineered cells, bioprocesses used 
      to expand cells, and improved supply chains are still complex and costly. To 
      overcome drawbacks associated with CAR-T technologies, novel CAR designs have 
      been used to genetically engineer cells derived from alpha beta (alphabeta) T cells, 
      other immune cells such as natural killer (NK) cells, gamma delta (gammadelta) T cells, 
      macrophages or dendritic cells. This review endeavours to trigger ideas on the 
      next generation of CAR-engineered cell therapies beyond CAR-T cells and, thus, 
      will enable effective, safe and affordable therapies for clinical management of 
      cancer. To achieve this, we present a multidisciplinary overview, addressing a 
      wide range of critical aspects: CAR design, development and manufacturing 
      technologies, pharmacological concepts and clinical applications of 
      CAR-engineered cell therapies. Each of these fields employs a large number of 
      ground-breaking scientific advances, where coordinated and complex process and 
      product development occur at their interfaces.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Luginbuehl, Vera
AU  - Luginbuehl V
AD  - Novartis Oncology, Cell & Gene Therapy, Novartis Pharma Schweiz AG, Rotkreuz, 
      Switzerland. Electronic address: vera.luginbuehl@novartis.com.
FAU - Abraham, Eytan
AU  - Abraham E
AD  - Personalized Medicine Lonza Pharma&Biotech, Lonza Ltd., Walkersville, MD, USA.
FAU - Kovar, Karin
AU  - Kovar K
AD  - daspool, Wadenswil, Switzerland.
FAU - Flaaten, Richard
AU  - Flaaten R
AD  - Novartis Oncology, Cell & Gene Therapy, Novartis Norge AS, Oslo, Norway.
FAU - Muller, Antonia M S
AU  - Muller AMS
AD  - Department of Medical Oncology and Hematology, University Hospital Zurich, 
      Zurich, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220209
PL  - England
TA  - Biotechnol Adv
JT  - Biotechnology advances
JID - 8403708
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - Leukocytes, Mononuclear
MH  - *Neoplasms/therapy
MH  - *Receptors, Chimeric Antigen/genetics
MH  - T-Lymphocytes
MH  - Tumor Microenvironment
OTO - NOTNLM
OT  - Advanced manufacturing technologies
OT  - CAR discovery and development
OT  - CAR pharmacology
OT  - CAR-T cell therapy
OT  - Chimeric antigen receptor (CAR)
OT  - Clinical trials
OT  - Genetic Engineering
OT  - Macrophages
OT  - Natural killer cells
OT  - cancer immunotherapy
EDAT- 2022/02/13 06:00
MHDA- 2022/05/18 06:00
CRDT- 2022/02/12 05:29
PHST- 2021/09/30 00:00 [received]
PHST- 2022/01/30 00:00 [revised]
PHST- 2022/02/01 00:00 [accepted]
PHST- 2022/02/13 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/02/12 05:29 [entrez]
AID - S0734-9750(22)00013-1 [pii]
AID - 10.1016/j.biotechadv.2022.107917 [doi]
PST - ppublish
SO  - Biotechnol Adv. 2022 Sep;58:107917. doi: 10.1016/j.biotechadv.2022.107917. Epub 
      2022 Feb 9.