Ex vivo-activated MHC-unrestricted immune effectors for cancer adoptive immunotherapy

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4 Citations (Scopus)

Abstract

Adoptive immunotherapy is considered a promising strategy for the treatment of metastatic tumors and current research efforts are directed to define the optimal approach and facilitate the transferability from preclinical to clinical settings. Among several approaches it is possible to schematically distinguish strategies based on either MHC-restricted or MHC-unrestricted immune effectors. The first are mainly based on the infusion of tumor-specific T lymphocytes capable of recognizing determined MHC-restricted tumor associated antigens (TAA) through their T cell receptor. MHC-unrestricted approaches do not target specific tumor associated antigens and are mainly mediated by effectors of the innate immune system, like natural killer (NK) cells or NKT cells, first barrier against pathogens and tumorigenesis processes, or by ex vivo activated lymphocytes like cytokine-induced killer (CIK) cells. MHC-unrestricted effectors are usually more abundant than TAA-specific precursors and easier to expand. Furthermore their activity is not restricted to precise HLA-haplotypes, not limited to a single tumor histotype and could overcome downregulation of MHC molecules operated by tumor cells as immune escape mechanism. In this review we will discuss the main cancer immunotherapy strategies based on MHC-unrestricted immune effectors. The topic will be approached from the angle of ex vivo expansion protocols in clinical prospective, as well as potential approaches to favorably modulate their functions.

Original languageEnglish
Pages (from-to)211-222
Number of pages12
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume14
Issue number2
DOIs
Publication statusPublished - 2014

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Adoptive Immunotherapy
Neoplasm Antigens
Neoplasms
Cytokine-Induced Killer Cells
Natural Killer T-Cells
Clinical Protocols
T-Cell Antigen Receptor
Natural Killer Cells
Immunotherapy
Haplotypes
Immune System
Carcinogenesis
Down-Regulation
Lymphocytes
T-Lymphocytes
Research

Keywords

  • Adoptive immunotherapy
  • CIK
  • MHC-unrestricted activity
  • NK
  • NKT

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Pharmacology

Cite this

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abstract = "Adoptive immunotherapy is considered a promising strategy for the treatment of metastatic tumors and current research efforts are directed to define the optimal approach and facilitate the transferability from preclinical to clinical settings. Among several approaches it is possible to schematically distinguish strategies based on either MHC-restricted or MHC-unrestricted immune effectors. The first are mainly based on the infusion of tumor-specific T lymphocytes capable of recognizing determined MHC-restricted tumor associated antigens (TAA) through their T cell receptor. MHC-unrestricted approaches do not target specific tumor associated antigens and are mainly mediated by effectors of the innate immune system, like natural killer (NK) cells or NKT cells, first barrier against pathogens and tumorigenesis processes, or by ex vivo activated lymphocytes like cytokine-induced killer (CIK) cells. MHC-unrestricted effectors are usually more abundant than TAA-specific precursors and easier to expand. Furthermore their activity is not restricted to precise HLA-haplotypes, not limited to a single tumor histotype and could overcome downregulation of MHC molecules operated by tumor cells as immune escape mechanism. In this review we will discuss the main cancer immunotherapy strategies based on MHC-unrestricted immune effectors. The topic will be approached from the angle of ex vivo expansion protocols in clinical prospective, as well as potential approaches to favorably modulate their functions.",
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AU - Giraudo, Lidia

AU - Carnevale-Schianca, Fabrizio

AU - Aglietta, Massimo

AU - Sangiolo, Dario

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