Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Apr 21;5(1):vdad044.
doi: 10.1093/noajnl/vdad044. eCollection 2023 Jan-Dec.

Convection-enhanced delivery of immunomodulatory therapy for high-grade glioma

Colin P Sperring  1 , Michael G Argenziano  1 , William M Savage  1 , Damian E Teasley  1 , Pavan S Upadhyayula  1 , Nathan J Winans  1 , Peter Canoll  2 , Jeffrey N Bruce  1
Affiliations
Review

Convection-enhanced delivery of immunomodulatory therapy for high-grade glioma

Colin P Sperring et al. Neurooncol Adv. .

Abstract

The prognosis for glioblastoma has remained poor despite multimodal standard of care treatment, including temozolomide, radiation, and surgical resection. Further, the addition of immunotherapies, while promising in a number of other solid tumors, has overwhelmingly failed in the treatment of gliomas, in part due to the immunosuppressive microenvironment and poor drug penetrance to the brain. Local delivery of immunomodulatory therapies circumvents some of these challenges and has led to long-term remission in select patients. Many of these approaches utilize convection-enhanced delivery (CED) for immunological drug delivery, allowing high doses to be delivered directly to the brain parenchyma, avoiding systemic toxicity. Here, we review the literature encompassing immunotherapies delivered via CED-from preclinical model systems to clinical trials-and explore how their unique combination elicits an antitumor response by the immune system, decreases toxicity, and improves survival among select high-grade glioma patients.

Keywords: convection-enhanced delivery; drug delivery; glioma; immunotherapy.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Diversity of immunotherapies delivered via CED in high-grade glioma.
See this image and copyright information in PMC

References

    1. Kanu OO, Mehta A, Di C, et al. . Glioblastoma multiforme: a review of therapeutic targets. Expert Opin Ther Targets. 2009;13(6):701–718. - PubMed
    1. Stupp R, Hegi ME, Mason WP, et al. ; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–466. - PubMed
    1. Zhu H, Leiss L, Yang N, et al. . Surgical debulking promotes recruitment of macrophages and triggers glioblastoma phagocytosis in combination with CD47 blocking immunotherapy. Oncotarget. 2017;8(7):12145–12157. - PMC - PubMed
    1. Misra A, Ganesh S, Shahiwala A, Shah SP.. Drug delivery to the central nervous system: a review. J Pharm Pharm Sci. 2003;6(2):252–273. - PubMed
    1. Bobo RH, Laske DW, Akbasak A, et al. . Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci U S A. 1994;91(6):2076–2080. - PMC - PubMed

LinkOut - more resources