Asset Details
Do you wish to reserve the book?
Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
Do you wish to request the book?
Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Diverse immunotherapies can effectively treat syngeneic brainstem tumors in the absence of overt toxicity
2019
Overview
Background
Immunotherapy has shown remarkable clinical promise in the treatment of various types of cancers. However, clinical benefits derive from a highly inflammatory mechanism of action. This presents unique challenges for use in pediatric brainstem tumors including diffuse intrinsic pontine glioma (DIPG), since treatment-related inflammation could cause catastrophic toxicity. Therefore, the goal of this study was to investigate whether inflammatory, immune-based therapies are likely to be too dangerous to pursue for the treatment of pediatric brainstem tumors.
Methods
To complement previous immunotherapy studies using patient-derived xenografts in immunodeficient mice, we developed fully immunocompetent models of immunotherapy using transplantable, syngeneic tumors. These four models – HSVtk/GCV suicide gene immunotherapy, oncolytic viroimmunotherapy, adoptive T cell transfer, and CAR T cell therapy – have been optimized to treat tumors outside of the CNS and induce a broad spectrum of inflammatory profiles, maximizing the chances of observing brainstem toxicity.
Results
All four models achieved anti-tumor efficacy in the absence of toxicity, with the exception of recombinant vaccinia virus expressing GMCSF, which demonstrated inflammatory toxicity. Histology, imaging, and flow cytometry confirmed the presence of brainstem inflammation in all models. Where used, the addition of immune checkpoint blockade did not introduce toxicity.
Conclusions
It remains imperative to regard the brainstem with caution for immunotherapeutic intervention. Nonetheless, we show that further careful development of immunotherapies for pediatric brainstem tumors is warranted to harness the potential potency of anti-tumor immune responses, despite their possible toxicity within this anatomically sensitive location.
Publisher
BioMed Central,BioMed Central Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
Subject
/ Antigens
/ Brain Stem Neoplasms - genetics
/ Brain Stem Neoplasms - immunology
/ Brain Stem Neoplasms - therapy
/ Cancer
/ Clinical/Translational Cancer Immunotherapy
/ Diffuse Intrinsic Pontine Glioma - immunology
/ Diffuse Intrinsic Pontine Glioma - therapy
/ Female
/ Genes
/ Genetic Therapy - adverse effects
/ Glioma
/ Gliomas
/ Granulocyte-Macrophage Colony-Stimulating Factor - genetics
/ Humans
/ Immunotherapy, Adoptive - adverse effects
/ Immunotherapy, Adoptive - methods
/ Kinases
/ Medicine
/ Melanoma
/ Mice
/ Oncology
/ Oncolytic Virotherapy - adverse effects
/ Oncolytic Virotherapy - methods
/ Suicide
/ T cells
/ T-Lymphocytes - transplantation
/ Toxicity
/ Tumors
/ Vaccinia
/ Viruses
