Protein- and DNA-based active immunotherapy targeting interleukin-13 receptor alpha2.
High-grade astrocytoma (HGA) is an invariably fatal malignancy with a mean survival of 14 months despite surgery, radiation, and chemotherapy. We have found that a restricted receptor for interleukin-13 (IL-13), IL-13 receptor alpha 2 (IL13Ralpha2), is abundantly overexpressed in the vast majority of HGAs but is not appreciably expressed in normal tissue, with the exception of the testes. Therefore, IL-13Ralpha2 is a very attractive target for anti-HGA immunotherapy. In order to test protein and genetic vaccines that target IL13Ralpha2, we developed a G26-IL13Ralpha2-expressing syngeneic immunocompetent murine glioma model. Using this glioma model, mice were immunized with recombinant extracellular IL13Ralpha2 protein (IL13Ralpha2ex) or a DNA expression vector containing the gene for IL13Ralpha2 and were subsequently challenged with IL13Ralpha2( + ) G26 tumors. Mice immunized with either recombinant or genetic IL13Ralpha2, but not mock-immunized controls, demonstrated complete protection against IL13Ralpha2( + ) glioma growth and mortality. Of interest, only the recombinant-protein-based vaccines generated detectable anti-IL13Ralpha2 antibodies. These studies demonstrate the in vivo efficiency of protein- and DNA-based immunotherapy strategies that target IL13Ralpha2 that may play a clinical role to eradicate the residual microscopic HGA cells that inevitably cause disease recurrence and mortality.
Mintz
Akiva
A
Brain Tumor Center of Excellence, Department of Neurosurgery & Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1082, USA. akiva.mintz@systrend.com
Gibo
Denise M
DM
Madhankumar
A B
AB
Cladel
Nancy M
NM
Christensen
Neil D
ND
Debinski
Waldemar
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001345:Autoradiography / Q000379:methods; D016466:CHO Cells; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000737:chemistry; D012008:Recurrence; D019444:Vaccines, DNA / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D053663:Interleukin-13 Receptor alpha2 Subunit; D011994:Recombinant Proteins; D019444:Vaccines, DNA