HOPP CHILDREN’S CANCER CENTER (KiTZ) AND THE GERMAN CANCER RESEARCH CENTER (DKFZ)

Combining CRISPR and AAV to selectively target oncogene-driven pediatric brain tumors

Drs. Marc Zuckermann and Lena Kutscher are working together with Drs. Stefan Pfister and David Jones to establish a new system for targeting oncogenic mutations in pediatric brain tumors at the Hopp Children’s Cancer Center (KiTZ) and the German Cancer Research Center (DKFZ) in Heidelberg, Germany. Our project’s objective is to combine tumor-specific CRISPR genome editing with tumor cell specific viral delivery.

This strategy applies to non-“druggable” oncogenes and should be unsusceptible to many known resistance mechanisms. As an initial proof-of-concept, we are focusing on BRAF(V600E)-driven pleomorphic xanthoastrocytoma (PXA) and H3.3(K27M)-driven diffuse intrinsic pontine glioma (DIPG) tumors. Both of these tumor types presumably rely on the mutated oncogene for survival. By combining tumor cell specific viral variants with oncogene-specific CRISPR molecules, we aim to establish a sufficiently precise gene therapy to treat patients with a therapeutically-relevant and safe viral dose. We will evaluate this approach for its treatment potential in a preclinical in vivo setting compared with standard-of-care therapy.

Our Research Partnerships

To date, Ian’s Friends Foundation has committed millions of dollars toward pediatric brain tumor research at the cutting-edge research institutions listed below.

Long-term goal is to improve understanding of tumor metabolism to design more effective therapies.
Long-term goal is to improve understanding of tumor metabolism to design more effective therapies.
New biorepository will provide the technology to grow and store cancer cells for use in brain tumor research.
New biorepository will provide the technology to grow and store cancer cells for use in brain tumor research.
Together, these Atlanta institutions pioneer the use of nanotechnology to gauge tumor size, stop tumor growth, and shrink tumors.
Together, these Atlanta institutions pioneer the use of nanotechnology to gauge tumor size, stop tumor growth, and shrink tumors.
Research focused on uncovering the mechanisms by which gene fusions contribute to tumor formation in pediatric low grade gliomas.
Research focused on uncovering the mechanisms by which gene fusions contribute to tumor formation in pediatric low grade gliomas.
Objective is to determine if an electrical stimulations regimen can arrest the division of dividing brain tumor cells.
Objective is to determine if an electrical stimulations regimen can arrest the division of dividing brain tumor cells.
Working to find biomarkers for brain tumors to make the diagnosis of tumor types easier, track their growth or even, no recurrence.
Working to find biomarkers for brain tumors to make the diagnosis of tumor types easier, track their growth or even, no recurrence.
Research establishing the feasibility of using interstitial infusion for treating pediatric brain stem gliomas. FDA approved clinical trial underway.
Research establishing the feasibility of using interstitial infusion for treating pediatric brain stem gliomas. FDA approved clinical trial underway.
Research focused on proteins which are active in pediatric low-grade gliomas. From this research, NYU hopes to better select molecular targeted drugs directed at these pathways.
Research focused on proteins which are active in pediatric low-grade gliomas. From this research, NYU hopes to better select molecular targeted drugs directed at these pathways.
Research focused on using new brain imaging techniques to improve diagnosis, prognosis and treatment of pediatric brain tumors.
Research focused on using new brain imaging techniques to improve diagnosis, prognosis and treatment of pediatric brain tumors.
Partnership between a physician and research scientist is examining innovative drug delivery methods for children with brain tumors.
Partnership between a physician and research scientist is examining innovative drug delivery methods for children with brain tumors.
This groundbreaking project could be the first step for the development of a variety of attractive modalities targeting therapeutic approaches beyond immunotherapy.
This groundbreaking project could be the first step for the development of a variety of attractive modalities targeting therapeutic approaches beyond immunotherapy.
Discovery regarding cancer cells' ability to hijack the brain's nerves could lead to new treatment avenues for aggressive brain tumors.
Discovery regarding cancer cells' ability to hijack the brain's nerves could lead to new treatment avenues for aggressive brain tumors.
Developing a strategy to ensure rapid translation of new drug candidates into clinical trials of medulloblastomas is a collaborative effort.
Developing a strategy to ensure rapid translation of new drug candidates into clinical trials of medulloblastomas is a collaborative effort.
University of Michigan Researchers aim to treat Pediatric Brain Tumors through the combination of Gene and Immune Therapy.
University of Michigan Researchers aim to treat Pediatric Brain Tumors through the combination of Gene and Immune Therapy.
Researchers at Johns Hopkins All Children’s and Johns Hopkins University hypothesize that a group of lncRNAs, including lncRNA HLX2-7, are key molecular signatures (biomarkers) and therapeutic targets for Group III medulloblastoma in children.
Researchers at Johns Hopkins All Children’s and Johns Hopkins University hypothesize that a group of lncRNAs, including lncRNA HLX2-7, are key molecular signatures (biomarkers) and therapeutic targets for Group III medulloblastoma in children.
Scientists work to establish a new system for targeting oncogenic mutations in pediatric brain tumors.
Scientists work to establish a new system for targeting oncogenic mutations in pediatric brain tumors.
Through a new collaboration between Duke and UNC Chapel Hill, our team is working on a radical new approach that combines living tissue brain slices with patient biopsies to recapitulate the clinical brain cancer phenotype.
Through a new collaboration between Duke and UNC Chapel Hill, our team is working on a radical new approach that combines living tissue brain slices with patient biopsies to recapitulate the clinical brain cancer phenotype.
The goal of this project is to dissect the cellular and molecular determinants required for human pediatric low grade astrocytoma (PLGA) engraftment as a means of developing robust and reproducible patient-derived tumor models.
The goal of this project is to dissect the cellular and molecular determinants required for human pediatric low grade astrocytoma (PLGA) engraftment as a means of developing robust and reproducible patient-derived tumor models.