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Create a Pediatric Immunotherapy Discovery and Development Network (PI-DDN)

NCI has announced several funding opportunities that align with the Cancer Moonshot.

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Immunotherapy makes use of the immune system to recognize and destroy infected, damaged, and transformed cells. This type of cancer treatment enhances the activity of immune cells to attack tumors. While immunotherapeutic approaches have been used successfully to treat a limited number of childhood cancers, particularly leukemia and neuroblastoma, there are currently no effective immunotherapy options for most patients with high-risk or difficult-to-treat childhood cancers.

There are a number of barriers to the development of immunotherapies for childhood cancers. Unlike many adult tumors, many childhood cancers express few or no markers that can be recognized by the immune system. Similarly, many immunotherapies target specific markers that are expressed in adult cancers but not childhood cancers. Also, tumors that develop in children can develop microenvironments that suppress the immune system and reduce the effectiveness of immunotherapies.

This recommendation is aimed at creating a pediatric immunotherapy science network that will focus on a collaborative effort to discover targets for immunotherapies and develop and test new treatment approaches, including cancer vaccines, cellular therapy, and combinations of immunotherapy and other forms of therapy.

Ultimately, the hope is to develop new immunotherapies and improve the effectiveness of current immunotherapy treatments to reduce the burden of cancer in children.

The Pediatric Immunotherapy Discovery and Development Network (PI-DDN)

This collaborative network is identifying and advancing preclinical immunotherapy research for children and adolescents with cancer. The network is working to discover and characterize new targets for immunotherapies, design experimental models to test the effectiveness of pediatric immunotherapies, develop new pediatric immunotherapy treatments, and improve the understanding of tumor immunity in children and adolescents with cancer. PI-DDN is also working to overcome major barriers in developing effective immunotherapies for children and adolescents, such as lower levels of proteins in tumor cells that can be recognized by immune cells and the immunosuppressive environments of tumors in some pediatric cancers.

Investigators in the PI-DDN are working together on multicomponent research studies centered around a pediatric cancer research area and individual pediatric immunotherapy projects. The goal of the network is to advance pediatric immunotherapies to treat children and adolescents with high-risk cancers.

Highlights of PI-DDN Research Progress

A PI-DDN research team has made advances in understanding and overcoming immune cell exhaustion to improve the cancer-fighting ability of CAR T-cells.

PI-DDN researchers are also identifying molecules on the surface of cancer cells that can be targets of new immune-based therapies. For example, there have been promising results using CAR T cells that are engineered to target the GPC2 protein in pediatric brain tumors.

Another team of PI-DDN researchers identified immune signatures of acute myeloid leukemia (AML) that are predictive of chemotherapy and immunotherapy response and resistance. Understanding these AML subtypes could inform the delivery of personalized therapies for children with cancer.

The PI-DDN program has been instrumental in building relationships and collaborations within the network, with other Cancer Moonshot initiatives, and with the broader research community. The steering committee includes a patient advocate and other associate members in its meetings. Through the creation of this network, the field of immunotherapy and immunoprevention research for childhood cancers has expanded and accelerated. 

Pediatric Immunotherapy Projects Awarded Cancer Moonshot Funding

Awarded Projects
Funding Opportunity Project Title Institution Principal Investigator(s)
Pediatric Immunotherapy Discovery and Development Network (PI-DDN) (U01) Multispecific Targeting Incorporating Cytokine Receptor Pathways in High Risk Pediatric Acute Leukemias to Improve Durability of Adoptive Cell Therapy-Induced Remissions University of Colorado Denver Fry, Terry J; Tasian, Sarah Kathleen
Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma Fred Hutchinson Cancer Research Center Olson, James M; Mehlin, Christopher
Dual Targeting of Tumoral Microenvironment and Tumoral Cells by Blocking the Il-33/St2 Pathway Indiana University - Purdue University at Indianapolis Paczesny, Sophie; Cheung, Nai-Kong V
Cassette Exons in Neoplastic Pro-B-Cells: Implications for Immunotherapy Children's Hospital of Philadelphia Thomas-Tikhonenko, Andrei; Barash, Yoseph
Metabolic Reprogramming of Tumor Microenvironment to Maximize Immunotherapy for Pediatric Cancers Research Institute Nationwide Children's Hospital Wang, Ruoning
Pediatric Immunotherapy Discovery and Development Network (PI-DDN) (U54) Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood Cancers Children's Hospital of Philadelphia Maris, John M; Mackall, Crystal
Cancer Immunotherapy Trials Network (CITN) (UM1) Cancer Immunotherapy Trials Network Central Operations And Statistical Center Fred Hutchinson Cancer Research Center Cheever, Martin Alexander
Pediatric Immunotherapy Discovery 
and Development Network (PI-DDN)(U54 - Clinical Trial Not Allowed)
Pediatric Ohio-New York Cancer (Peds-ONC) Immunotherapy Center Research Inst Nationwide Children'S Hosp Cripe, Timothy P; Mardis, Elaine R
Pediatric Immunotherapy Discovery 
and Development Network (PI-DDN)(U01 - No Clinical Trial Allowed)
Defining and overcoming intrinsic T cell dysfunction to enable pediatric immunotherapy
Children's Hosp Of Philadelphia Barrett, David M; Grupp, Stephan A
Advancing Cancer Immunotherapy by Mitigating Immune-Related Adverse Events (irAE) (U01) Adrenergic Modulation of Cellular Immune Functions in CAR T Cell-Induced Cytokine Release Syndrome Johns Hopkins University Staedtke, Verena; Bai, Renyuan
Humoral Immunity After CAR-T Cell Therapy for B Cell Malignancies: The HICAR Study Fred Hutchinson Cancer Research Center Hill, Joshua Aiden
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