Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy.
Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor-modified T cells and phase III clinical trials for IL-13-conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Bart
B
Thaci
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Christine E
CE
Brown
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Emanuela
E
Binello
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Katherine
K
Werbaneth
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Prakash
P
Sampath
Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).
Sadhak
S
Sengupta
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D005098:Exotoxins / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000627:therapeutic use; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology / Q000627:therapeutic use*; D008081:Liposomes / Q000627:therapeutic use; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D011993:Recombinant Fusion Proteins; D016896:Treatment Outcome
D005098:Exotoxins; C521502:IL13-PE38; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D008081:Liposomes; D011993:Recombinant Fusion Proteins
IL13Rα2; glioblastoma; glioma; immunotherapy; toxin