TY - JOUR
T1 - Ex vivo-activated MHC-unrestricted immune effectors for cancer adoptive immunotherapy
AU - Leuci, Valeria
AU - Mesiano, Giulia
AU - Gammaitoni, Loretta
AU - Todorovic, Maja
AU - Giraudo, Lidia
AU - Carnevale-Schianca, Fabrizio
AU - Aglietta, Massimo
AU - Sangiolo, Dario
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Adoptive immunotherapy
KW - CIK
KW - MHC-unrestricted activity
KW - NK
KW - NKT
UR - http://www.scopus.com/inward/record.url?scp=84893483837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893483837&partnerID=8YFLogxK
U2 - 10.2174/18715206113136660371
DO - 10.2174/18715206113136660371
M3 - Article
C2 - 24237224
AN - SCOPUS:84893483837
VL - 14
SP - 211
EP - 222
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
SN - 1871-5206
IS - 2
ER -