PMID- 37993172
OWN - NLM
STAT- MEDLINE
DCOM- 20231211
LR  - 20240123
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Linking)
VI  - 27
IP  - 11
DP  - 2023 Jul-Dec
TI  - Interleukin-18 in cancer immunology and immunotherapy.
PG  - 1035-1042
LID - 10.1080/14728222.2023.2287574 [doi]
AB  - INTRODUCTION: Interleukin-18 (IL-18) is a myeloid leukocyte inflammatory mediator 
      whose main known function is to elicit IFNgamma secretion from T and NK cells. AREAS 
      COVERED: This function offers potential in cancer immunotherapy but as a single 
      treatment, preclinical and clinical antitumor activities are modest. IL-18 
      bioactivity is chiefly downregulated by a decoy soluble receptor named 
      IL18-binding protein (IL-18BP) that is induced by IFNgamma as a negative feedback 
      mechanism. Recent advances indicate promising efficacy of IL-18 at armoring CAR-T 
      cells for the treatment of hematological malignancies. Preclinical research has 
      also yielded IL-18 constructs that do not bind IL-18BP but have preserved 
      activity on the receptor and exert markedly increased antitumor effects. Indeed, 
      agents of this kind are undergoing clinical trials. The synergistic effects of 
      IL-18 and IL-12 in combination to induce IFNgamma are extremely potent but are toxic 
      if systemically delivered. In mouse models, IL-12 and decoy-resistant variants of 
      IL-18 can be efficaciously used as local treatments for tumors by exploiting mRNA 
      intratumoral co-delivery. Moreover, antitumor T cells can be transiently 
      engineered with mRNAs encoding this combination of cytokines to attain 
      efficacious synergistic effects also upon intratumoral delivery. EXPERT OPINION: 
      IL-18 certainly holds promise for immunotherapy in combination with other agents 
      and for local approaches.
FAU - Cirella, Assunta
AU  - Cirella A
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
FAU - Olivera, Irene
AU  - Olivera I
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
FAU - Luri-Rey, Carlos
AU  - Luri-Rey C
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
FAU - Bolanos, Elixabet
AU  - Bolanos E
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
FAU - Berraondo, Pedro
AU  - Berraondo P
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Spain.
FAU - Melero, Ignacio
AU  - Melero I
AD  - Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 
      Spain.
AD  - Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Cancer (CIBERONC), Spain.
AD  - Department of Immunology and immunotherapy, Clinica Universidad de Navarra, 
      Pamplona, Spain.
AD  - Department of oncology, Clinica Universidad de Navarra, Madrid, Spain.
AD  - Centro del Cancer de la Universidad de Navarra (CCUN), Pamplona, Spain.
AD  - Nuffield Department of Medicine (NDM), University of Oxford, Oxford, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231207
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
RN  - 0 (Interleukin-18)
RN  - 187348-17-0 (Interleukin-12)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Interleukin-18
MH  - Immunotherapy
MH  - *Neoplasms/therapy
MH  - Interleukin-12
MH  - Cytokines
OTO - NOTNLM
OT  - CAR-T cells
OT  - Interleukin-18
OT  - combination strategies
OT  - decoy resistant IL-18
OT  - mRNA
EDAT- 2023/11/23 00:42
MHDA- 2023/12/11 12:42
CRDT- 2023/11/22 20:53
PHST- 2023/12/11 12:42 [medline]
PHST- 2023/11/23 00:42 [pubmed]
PHST- 2023/11/22 20:53 [entrez]
AID - 10.1080/14728222.2023.2287574 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2023 Jul-Dec;27(11):1035-1042. doi: 
      10.1080/14728222.2023.2287574. Epub 2023 Dec 7.