Sammy's donated
to in 2024
Crazy 8 Initiative Awards
Crazy 8 Initiative Awards fund research into innovative and rigorous approaches that directly
address the most intractable issues in pediatric cancer research today. This award is designed to coalesce crossdisciplinary cores of scientists working collaboratively in order to accelerate the pace of
discovering new cures
Understanding and Inhibiting Mechanisms of Metastatic Spread in Osteosarcoma
Principal Investigator:
Dr. Alejandro E. Sweet-Cordero
Institution:
The Regents of the University of California, San Francisco
Type of Cancer:
Osteosarcoma
Grant Amount:
Roughly $5,000,000 over multiple years
Targeting the Biological Underpinnings of Pulmonary Metastasis in Osteosarcoma
Principal Investigator:
Dr. Rani E. George
Institution:
Dana-Farber Cancer Institute
Type of Cancer:
Osteosarcoma
Grant Amount:
Roughly $5,000,000 over multiple years
“A” Awards
The ‘A’ Award is designed for the early independent career scientist who wants to establish a career in pediatric oncology research.
Circulating Tumor Biomarkers: New Paradigms for Management of Neuroblastoma
Principal Investigator:
Dr. Mark Applebaum
Institution:
The University of Chicago
Type of Cancer:
Neuroblastoma
Grant Amount:
$200,000 per year for four years
Turning Killers into THINKers: TME Hostility-Impervious NK cells for Treating Neuroblastoma and Sarcoma
Principal Investigator:
Dr. Robin Parihar
Institution:
Baylor College of Medicine
Type of Cancer:
Neuroblastoma
Grant Amount:
$200,000 per year for four years
Exploiting Glypican Diversity in Neuroblastoma Plasticity with Bicistronic CAR T Cell Targeting
Principal Investigator:
Dr. Kristopher Bosse
Institution:
The Children's Hospital of Philadelphia
Type of Cancer:
Neuroblastoma
Grant Amount:
$250,000 over two years
Crazy 8 Initiative Award:
Targeting the Biological Underpinnings of Pulmonary Metastasis in Osteosarcoma
This Crazy 8 Initiative Award began in 2022 and is in its third year of funding.
Principal Investigator:
Dr. Kristopher Bosse
Institution:
Institution: Dana-Farber Cancer Institute
Type of Cancer:
Neuroblastoma
Grant Amount:
Roughly $5,000,000 over multiple years
Summary of Project:
Abstract
Osteosarcoma is a bone tumor that affects children during their growth spurt. Treatment is difficult and has not improved in almost four decades. Most of the kids who die from osteosarcoma succumb to complications of lung metastasis. Therapies that prevent or treat metastatic disease may be the most impactful innovation that we could bring these children. There are currently three primary challenges that prevent us from improving outcomes in these patients: First, we know what the most common genetic changes in osteosarcoma are, but we know little about how these changes create cancer. The defining feature of osteosarcoma genomes is simply widespread rearrangement of chromosomes (like DNA going through a blender). Parsing the changes that result from this chaos has been difficult because all current sequencing strategies map experimental sequences onto a normal human genome, not the deeply rearranged osteosarcoma genome. As such, it becomes impossible to identify the real relationship between any two parts of the genome. Second, we understand little about the steps that drive the development of metastatic lesions. We know that each metastatic lesion is filled with a complex arrangement of highly abnormal immune and lung cells alongside tumor cells, which often look quite different one from another. However, we do not understand the process that transforms a single tumor cell stuck in the lung into this complex metastatic organ. Third, when we and others have identified potential drivers of metastasis, they are usually not druggable, negating any potential impact those discoveries might have on patients.
Project Goals
Our proposal will address each of these challenges. To unravel the effects that widespread genetic rearrangements have on malignant behavior, we will build reference genomes specific to each tumor. With these tumor-specific references, we will map out all the new connections formed by those rearrangements so that we can determine how each genetic switch becomes re-wired. With these genetic wiring diagrams in hand, we can begin to discover the ways that this cancer-specific re-wiring drives malignant behavior like metastasis. To uncover the processes that drive the development of metastatic lesions, we will employ a combination of
cutting-edge techniques that allow us to watch metastases develop cell-by-cell, observing changes in gene expression across the genome, from single disseminated tumor cells to complex metastatic lesions, being sensitive to the unique genetic wiring of each tumor. To overcome the challenges of draggability, we will leverage a newer technology, pioneered by members of our research team, to develop drugs that utilize things like molecular glues designed to stick to specific proteins, tagging them with signals that engage the recycling machinery of the cell, eliminating the protein by degrading it (reducing the protein to its nutrient parts). Beginning with a target that we have already identified and expanding to new targets as we learn more about the genetic re-wiring and mechanisms of metastasis, we will produce a new generation of metastasis-targeting candidate drugs. Successful prosecution of this plan could transform the therapeutic approach to patients with metastatic osteosarcoma and beyond.
Reach Award:
Circumventing Pediatric Solid Tumor Microenvironment Resistance by Combinatorial
CAR NK and Immunomodulating Therapy
This Reach Award began in 2023 and is in its second year of funding.
Principal Investigator:
Prof. Mitchell S Cairo
Institution:
New York Medical College
Type of Cancer:
Neuroblastoma
Grant Amount:
$250,000 over two years
Summary of Project:
Abstract
Childhood solid tumors are aggressive cancers in children and adolescents that often reoccur or progress after remission (relapsed) or do not even respond to current treatments (refractory). Over the past 40 years, despite multiple therapeutic approaches, children and adolescents with these relapsed/refractory cancers have a dismal outcome (less than 5% of them will survive 1 year) in large part due to the resistance to therapies induced by the suppressive environment in the tumor. New therapeutic approaches are urgently needed to improve the survival of these patients. Natural killer (NK) cell is a type of immune cell that fights cancer in children and
adolescents. Previous studies showed that the more active NK cells found in patients’ tumors, the longer the patients survived. In our previous research in immunotherapy against childhood solid tumors funded by the National Cancer Institute, we focused on engineering chimeric antigen receptor (CAR) NK cells to increase the ability of NK cells in specifically targeting cancer cells. Furthermore, we successfully developed a variety of effective therapeutic approaches by combining CAR NK cells with various immune modulators to further improve CAR NK cell anti-tumor activity and better overcome the resistance to NK cells in the suppressive tumor
environment. In this application, we plan to identify more effective therapies by rationally combining CAR NK cells with multiple immune modulators that we previously found to be effective and perform required FDA validations and approval for a clinical trial in children and adolescents with relapsed/refractory solid tumors soon after this grant is concluded.
Project Goals
Our project goals are 1) to improve tumor targeting and cancer cell killing abilities of natural killer (NK) cells by modifying NK cells with chimeric antigen receptor (CAR) against newly identified surface proteins on childhood solid tumors (ROR1, MCAM); 2) to facilitate CAR NK cells penetration into the tumor by further engineering CAR NK cells with a tumor-attracting surface protein (CXCR2); 3) to further improve the killing effect of CAR NK cells against tumor cells by combining a therapeutic anti-tumor antibody called dinutuximab; 4) to make tumor cells better recognized by CAR NK cells by modifying tumor cells with a drug named romidepsin; and 5) to increase
CAR NK cell half-life, number and activity by combining a novel agent (anti-CD16-IL15-anti-B7H3 TriKE) that connects tumor cells with NK cells and provides support for NK cell survival and persistence. By combining these therapeutic approaches that we previously tested individually to be effective, we hope to identify more effective CAR NK therapy against solid tumors in children and adolescents. We will next complete the required FDA validations and obtain the necessary approval from the FDA for a future clinical trial to
begin at the end of this grant cycle to eventually bring this new therapy into the clinic. If successful, our study will identify an optimal
combinatorial NK cell-based immunotherapy that overcomes the suppressive environment in solid tumors and may ultimately
lead to the delivery of a highly effective immunotherapeutic regimen for the treatment of children and adolescents with childhood solid tumors.