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Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models by Scott Parker; Charlotte McDowall; Luis Sanchez-Perez; Cristina Osorio; Patrick C. Duncker; Aaron Briley; Adam M. Swartz; James E. Herndon; Yen-Rei A. Yu; Roger E. McLendon; Thomas F. Tedder; Annick Desjardins; David M. Ashley; Michael Dee Gunn; David S. Enterline; David A. Knorr; Ira H. Pastan; Smita K. Nair; Darell D. Bigner; Vidyalakshmi Chandramohan is a Medicine article available to read on EtoBox.
What is Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models about?
D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized that immunosuppression in glioblastoma limits D2C7-IT efficacy. To improve the response rate and reverse immunosuppression, we combined D2C7-IT tumor cell killing with αCD40 costimulation of antigen-presenting cells. In murine glioma models, a single intratumoral injection of D2C7-IT+αCD40 treatment activated a proinflammatory phenotype in microglia and macrophages, promoted long-term tumor-specific CD8 + T cell immunity, and generated cures. D2C7-IT+αCD40 treatment increased intratumoral Slamf6 + CD8 + T cells with a progenitor phenotype and decreased terminally exhausted CD8 + T cells. D2C7-IT+αCD40 treatment stimulated intratumoral CD8 + T cell proliferation and generated cures in glioma-bearing mice despite FTY720-induced peripheral T cell sequestration. Tumor transcriptome profiling established CD40 up-regulation, pattern recognition receptor, cell senescence, and immune response pathway activation as the drivers of D2C7-IT+αCD4
Who reads Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models?
It is typically read by researchers, students, and practitioners in Medicine.
- Author
- Scott Parker; Charlotte McDowall; Luis Sanchez-Perez; Cristina Osorio; Patrick C. Duncker; Aaron Briley; Adam M. Swartz; James E. Herndon; Yen-Rei A. Yu; Roger E. McLendon; Thomas F. Tedder; Annick Desjardins; David M. Ashley; Michael Dee Gunn; David S. Enterline; David A. Knorr; Ira H. Pastan; Smita K. Nair; Darell D. Bigner; Vidyalakshmi Chandramohan
- Publisher
- American Association for the Advancement of Science (AAAS)
- Published
- 2023
- Language
- EN
- Field
- Medicine (Life Sciences)