TY - JOUR
T1 - Overcoming the hurdles of autologous t‐cell‐based therapies in b‐cell non‐hodgkin lymphoma
AU - van Bruggen, Jaco A. C.
AU - Martens, Anne W. J.
AU - Tonino, Sanne H.
AU - Kater, Arnon P.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The next frontier towards a cure for B‐cell non‐Hodgkin lymphomas (B‐NHL) is autologous cellular immunotherapy such as immune checkpoint blockade (ICB), bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T‐cells. While highly successful in various solid malignancies and in aggressive B‐cell leukemia, this clinical success is often not matched in B‐ NHL. T‐cell subset skewing, exhaustion, expansion of regulatory T‐cell subsets, or other yet to be defined mechanisms may underlie the lack of efficacy of these treatment modalities. In this review, a systematic overview of results from clinical trials is given and is accompanied by reported data on T‐cell dysfunction. From these results, we distill the underlying pathways that might be responsible for the observed differences in clinical responses towards autologous T‐cell‐based cellular immunotherapy modalities between diffuse large B‐cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). By integration of the clinical and biological findings, we postulate strategies that might enhance the efficacy of autologous‐based cellular immunotherapy for the treatment of B‐ NHL.
AB - The next frontier towards a cure for B‐cell non‐Hodgkin lymphomas (B‐NHL) is autologous cellular immunotherapy such as immune checkpoint blockade (ICB), bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T‐cells. While highly successful in various solid malignancies and in aggressive B‐cell leukemia, this clinical success is often not matched in B‐ NHL. T‐cell subset skewing, exhaustion, expansion of regulatory T‐cell subsets, or other yet to be defined mechanisms may underlie the lack of efficacy of these treatment modalities. In this review, a systematic overview of results from clinical trials is given and is accompanied by reported data on T‐cell dysfunction. From these results, we distill the underlying pathways that might be responsible for the observed differences in clinical responses towards autologous T‐cell‐based cellular immunotherapy modalities between diffuse large B‐cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). By integration of the clinical and biological findings, we postulate strategies that might enhance the efficacy of autologous‐based cellular immunotherapy for the treatment of B‐ NHL.
KW - Bispecific antibodies
KW - B‐NHL
KW - CAR T‐cells
KW - CLL
KW - Immune checkpoint blockade
KW - Immunotherapy
KW - T‐cell dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85098256567&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers12123837
DO - https://doi.org/10.3390/cancers12123837
M3 - Article
C2 - 33353234
SN - 2072-6694
VL - 12
SP - 1
EP - 31
JO - Cancers
JF - Cancers
IS - 12
M1 - 3837
ER -