Neurosurgery Research

The MD Anderson Central Nervous System Tumor Analysis STream “CATALYST” is a streamlined, multi-departmental biospecimen collection and analysis pipeline that comprehensively analyzes and integrates data from every available
neurosurgical patient at MD Anderson. 

CATALYST is not only unique, but highly innovative as it enhances biospecimen-based research, empowering multiple investigational initiatives toward a comprehensive assessment of primary and recurrent nervous system tumors, with the inclusion of matched blood, cerebrospinal fluid, and stool specimens. Funded by the highly successful MD Anderson Moon Shots® Program, this effort is unique to MD Anderson, where we see more rare tumors than any other cancer center in the world. 

Main goals of CATALYST:

• Define signatures of brain tumors through genetic and epigenetic profiling.
• Better understand the limited activity of immunotherapy in brain tumors through detailed immune profiling of matched tumor and blood samples.
• Identify nervous system tumor biomarkers and develop non-invasive approaches to diagnose cancer and follow tumor progression by characterizing cerebrospinal fluid and blood samples.
• Characterize and correlate gut and tumor microbiomes to determine if and how the microbiome affects tumor biology, treatment responses and overall patient outcomes.

Specimen Distribution Information December 2021:

• Total Primary Brain Tumors: 224
• Total Skull Base Tumors: 150
• Secondary Brain Tumors: 100
• Spine and Peripheral Tumors: 80
• Miscellaneous: 32

A project that advances the use of genetically engineered natural killer (NK) cell therapy in treating glioblastoma. After learning how NK cells, a type of immune cell, are suppressed by the glioblastoma tumor microenvironment, the Moon Shot team is now creating NK cells that are genetically engineered to resist that immune suppression.

A project that will directly tackle the more rigorous vetting of agents that are identified in the discovery stage and considered promising for clinical trials. ACCELERATE will leverage multiple preclinical platforms to create a robust strategy for rigorous testing of novel agents so that definitive and confident Go/No-Go decisions can be made more efficiently.

The Moon Shot has successfully developed Delta-24-RGD, a cold virus engineered to infect and attack glioblastoma cells. Researchers are exploring the possibility of delivering the virus directly to the tumor using stem cells derived from bone marrow called mesenchymal stem cells (MSCs).

A translational research program funded by the National Cancer Institute to enable the rapid and efficient movement of basic scientific findings into the clinical setting. Frederick Lang, M.D., PI, and Juan Fueyo, M.D., serve as the co-principle investigators. Research projects include:
 

• Oncolytic Adenoviruses for Glioma Therapy
• Off-the-shelf Genetically Engineered Natural Killer Therapy for Glioblastoma
  
• Deciphering Germline and Somatic Genomic Landscape of Gliomas in Black and Hispanic Minority Groups
  

• Specific Aim 1: Test the combination of Delta-24-RGD with anti-PD-1 antibodies in patients with recurrent malignant gliomas.
• Specific Aim 2: Assess the safety and biological effects of a next-generation Delta-24-RGD expressing OX40L in patients with recurrent glioma.
  
• Specific Aim 3: Characterize the antiglioma-potency elicited by Delta-24-RGDOX, Delta-24-GREAT, Delta-24-ACT and their combinations. 
  

• Specific Aim 1:  To initiate a Phase 1/II study of the safety and efficacy of TGF-βR2-/NR3C1-CB-NK cells in relapsed/recurrent GBM.
• Specific Aim 2: Study the fate of TGF-βR2-/NR3C1-CB-NK cells and associated immune changes in the CNS and correlate the findings with disease response.  
  
• Specific Aim 3: Determine if the membrane-anchored IL-12, IL-21 or IL-15 can further increase the persistence and potency of TGF-βR2-/NR3C1-CB-NK cells against GBM without undue toxicity.
  

• Specific Aim 1: Characterize the somatic genomic landscape of gliomas in Black and Hispanic patients.
• Specific Aim 2: Determine the extent to which racial and ethnic composition in Blacks and Hispanics correlates with disease-defining molecular alterations.
• Specific Aim 3: Evaluate the extent to which germline and the somatic variation in Blacks and Hispanics impacts clinical outcome.