PMID- 37813764
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240408
IS  - 1879-0305 (Electronic)
IS  - 1359-6101 (Linking)
VI  - 75
DP  - 2024 Feb
TI  - Bioengineering strategies to enhance the interleukin-18 bioactivity in the modern 
      toolbox of cancer immunotherapy.
PG  - 65-80
LID - S1359-6101(23)00070-9 [pii]
LID - 10.1016/j.cytogfr.2023.09.005 [doi]
AB  - Cytokines are the first modern immunotherapeutic agents used for activation 
      immunotherapy. Interleukin-18 (IL-18) has emerged as a potent anticancer 
      immunostimulatory cytokine over the past three decades. IL-18, structurally is a 
      stable protein with very low toxicity at biological doses. IL-18 promotes the 
      process of antigen presentation and also enhances innate and acquired immune 
      responses. It can induce the production of proinflammatory cytokines and increase 
      tumor infiltration of effector immune cells to revert the immunosuppressive 
      milieu of tumors. Furthermore, IL-18 can reduce tumorigenesis, suppress tumor 
      angiogenesis, and induce tumor cell apoptosis. These characteristics present 
      IL-18 as a promising option for cancer immunotherapy. Although several 
      preclinical studies have reported the immunotherapeutic potential of IL-18, 
      clinical trials using it as a monotherapy agent have reported disappointing 
      results. These results may be due to some biological characteristics of IL-18. 
      Several bioengineering approaches have been successfully used to correct its 
      defects as a bioadjuvant. Currently, the challenge with this anticancer 
      immunotherapeutic agent is mainly how to use its capabilities in a rational 
      combinatorial therapy for clinical applications. The present study discussed the 
      strengths and weaknesses of IL-18 as an immunotherapeutic agent, followed by 
      comprehensive review of various promising bioengineering approaches that have 
      been used to overcome its disadvantages. Finally, this study highlights the 
      promising application of IL-18 in modern combinatorial therapies, such as 
      chemotherapy, immune checkpoint blockade therapy, cell-based immunotherapy and 
      cancer vaccines to guide future studies, circumventing the barriers to 
      administration of IL-18 for clinical applications, and bring it to fruition as a 
      potent immunotherapy agent in cancer treatment.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Taheri, Mojtaba
AU  - Taheri M
AD  - Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Tehrani, Hossein Abdul
AU  - Tehrani HA
AD  - Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares 
      University, Tehran, Iran. Electronic address: h.tehrani@modares.ac.ir.
FAU - Daliri, Fatemeh
AU  - Daliri F
AD  - Gonabad University of Medical Sciences, Gonabad, Iran.
FAU - Alibolandi, Mona
AU  - Alibolandi M
AD  - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad 
      University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical 
      Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, 
      Mashhad, Iran.
FAU - Soleimani, Masoud
AU  - Soleimani M
AD  - Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat 
      Modares University, Iran.
FAU - Shoari, Alireza
AU  - Shoari A
AD  - Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
FAU - Arefian, Ehsan
AU  - Arefian E
AD  - Department of Microbiology, School of Biology, College of Science, University of 
      Tehran, Tehran, Iran; Pediatric Cell and Gene Therapy Research Center, Gene, Cell 
      & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 
      Electronic address: arefian@ut.ac.ir.
FAU - Ramezani, Mohammad
AU  - Ramezani M
AD  - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad 
      University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical 
      Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, 
      Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230928
PL  - England
TA  - Cytokine Growth Factor Rev
JT  - Cytokine & growth factor reviews
JID - 9612306
RN  - 0 (Interleukin-18)
RN  - 0 (Cytokines)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - Humans
MH  - Interleukin-18/therapeutic use
MH  - Immunotherapy/methods
MH  - *Neoplasms/therapy
MH  - Cytokines
MH  - *Antineoplastic Agents
MH  - Bioengineering
MH  - Interleukin-2
OTO - NOTNLM
OT  - CAR T cell
OT  - Cancer
OT  - Cell therapy
OT  - Cytokine engineering
OT  - Immunotherapy
OT  - Interleukine-18
COIS- Declaration of Competing Interest The authors declare that they have no competing 
      interests that could have appeared to influence the work reported in this paper.
EDAT- 2023/10/10 00:42
MHDA- 2024/02/16 06:42
CRDT- 2023/10/09 22:22
PHST- 2023/08/26 00:00 [received]
PHST- 2023/09/26 00:00 [revised]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2024/02/16 06:42 [medline]
PHST- 2023/10/10 00:42 [pubmed]
PHST- 2023/10/09 22:22 [entrez]
AID - S1359-6101(23)00070-9 [pii]
AID - 10.1016/j.cytogfr.2023.09.005 [doi]
PST - ppublish
SO  - Cytokine Growth Factor Rev. 2024 Feb;75:65-80. doi: 
      10.1016/j.cytogfr.2023.09.005. Epub 2023 Sep 28.