With support from the Heart of the Brain, the UCLA Brain Tumor Specialized Program Of Research Excellence (SPORE) has continued to address critical barriers to translational progress in brain cancer research, including major gaps in our knowledge about the basic biology of various types of gliomas and the development of treatment resistance that may lead to recurrence. Given the heterogeneous nature of malignant gliomas, a combination of diverse approaches will likely be needed in concert to overcome tumor treatment resistance. To effectively develop such combination therapeutic approaches, we need a better understanding of the varied fields of brain tumor immunology, tumor metabolism, cancer stem cells, and epigenetic targets in glioma. Our research labs address these critical areas of brain cancer biology with a diversity of translational approaches to innovatively and rationally tackle the problem of treatment resistance and brain tumor relapse.

Over past several years, we have maintained our stable and highly productive group of clinicians, scientists, and physician-scientists, while expanding our program to accelerate the pace of new scientific discoveries and facilitate translation of such discoveries to the clinic.  We have had significant accomplishments in several ongoing established projects and have provided start-up funding to some new junior investigators, such as Dr. Aparna Bhaduri, Dr. Kunal Patel, and Dr. Willy Hugo.

Dr. Aparna Bhaduri’s lab at UCLA is tackling brain cancer by uncovering how the same cellular programs that shape a baby’s brain become harmful when they reappear in brain tumors. They use cutting-edge tools like growing tiny, simplified organoids that model the human brain in dishes and exploring how tumor cells grow and change in this environment to map out which types of stem-like cells in the tumor are responsible for its growth, resistance to treatment, and recurrence. By comparing these tumor cells to normal brain development, they aim to identify how these stem cells make decisions and precisely which cells to target with new therapies.

Dr. Kunal Patel’s lab focuses on the detection and therapeutic targeting of invasive infiltrating glioblastoma tumor cells migrating from the main bulk of tumor. In collaboration with Dr. Benjamin Ellingson, Dr. Patel works on using advanced imaging techniques to visualize infiltrating tumor cells in humans.  In addition, Dr. Patel works on understanding the biology of infiltrative tumor cells to identify molecular targets for direct therapy to invasive tumor cells that cannot be removed at surgery. The results of this have yielded a new clinical trial on pH magnetic resonance imaging (MRI)-based surgery for infiltrating tumor resection.  This Phase 1 clinical trial has recently been opened for newly diagnosed and recurrent glioblastoma.

Dr. Willy Hugo’s lab aims to understand how immunotherapeutic approaches enhances survival in patients and to identify biomarkers linked to long-term anti-tumor immunity, with the goal of potentially improving the efficacy of immunotherapy in brain tumor patients.  Their lab uses high-dimensional computational biology techniques, including single-cell mRNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to map the immune architecture within tumors from exceptional long-term survivors and comparing them to short-term survivors receiving the same therapies.  The multiplex immunofluorescence (mIF) machine used to perform these studies was purchased using HOTB funds, and these studies would not have been possible without it.

Dr. Robert Prin’s lab studies the immune system and how to generate effective anti-tumor immune responses against brain tumors.  They utilize advanced technologies to understand what is impaired when brain tumors are growing, and then how immune-based therapies can reverse these defects and activate a particular type of immune cell, the killer T cell, to target and kill these tumor cells.  Pre-clinical models are used to study mechanisms in the lab and to test new combination therapies.

Dr. Linda Liau’s lab studies the clinical neuro-immunology of brain tumors, and in collaboration with Dr. Prins, translates the findings from pre-clinical animal models to perform IND-enabling studies that are then used to go to the FDA to initiate first-in-human early phase (Phase I) clinical trials in patients.  With the support of federal NIH grants and philanthropic donors like the HOTB, we have just completed our Phase I clinical trial testing the safety and immune responses in recurrent glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination with PD-1 antibody blockade.  Specifically, we are evaluating the anti-tumor immune responses in recurrent glioblastoma patients when PD-1 mAb blockade is given before or after ATL-DC vaccination.  In collaboration with Dr. Anthony Wang, we are also pursuing the development of a personalized mRNA tumor associated antigen-targeted DC vaccine for  pediatric and adolescent and young adult (AYA) brain tumors, which can hopefully be applied to patients like Isabel to prevent brain tumor progression and recurrence.