# Engaging and Enhancing Neuroblastoma Immune Targeting

> **NIH NIH U54** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $173,248

## Abstract

OVERALL SUMMARY/ABSTRACT
 There is a major paradox confronting the field of childhood cancer research. Several decades ago,
pioneering investigators focused on children with cancer led a revolution resulting in previously incurable
malignancies becoming curable. In contrast, over the last two decades, basic science has continued to
advance fundamental understanding of the oncogenesis of pediatric cancers, but cure rates for most pediatric
malignancies have plateaued, and the field has witnessed first-hand that current standard therapies often
saddle survivors with life threatening therapy-induced morbidities. It is sobering that for most children who
suffer relapse, few if any novel therapeutic options exist, and most patients receive the same type of therapy
that failed them in the first place. The funding opportunity arising out of the Beau Biden Cancer Moonshot
initiative directly addresses this paradox by forming a Pediatric Immunotherapy Discovery and Development
Network (PI-DDN). Immunotherapy for B-ALL and neuroblastoma is now credentialed, with CD19 directed
immunotherapies showing unprecedented activity in highly refractory cases of lymphoid malignancies. The
field is now poised for a focused and sustained multi-disciplinary effort to extend these early successes, and
rethink our approach to childhood cancer therapy in general. Here, we propose a pediatric immuno-oncology
Center entitled Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood
Cancers. We envision this Center providing a central hub for the PI-DDN, creating additional opportunities for
multi-disciplinary research with the common goal of creating new cancer immunotherapies for children. This
Center embodies three highly integrated multi-institutional Projects supported by a single Administrative and
Statistical Core. The overarching hypothesis to be tested here is that childhood cancers harbor lineage-specific
mechanisms of oncogenesis and immune evasion that can be precisely and effectively targeted by rationally
designed and developed immunotherapeutic regimens. Project 1 will discover lineage specific cell surface
molecules that have project-defined optimal attributes for synthetic immunotherapeutic based targeting, and
use this to create and credential new therapeutics based upon preclinical efficacy in high-risk childhood cancer
models. Project 2 will focus on major mechanisms of immunotherapy resistance by developing approaches to
circumvent the fundamental issues of intra- and inter-tumoral heterogeneity and T cell dysfunction due to both
intrinsic and extrinsic factors. Project 3 will focus on a major difference between pediatric and many adult
malignancies, with pediatric cancers typically eliciting little adaptive immunity, and develop approaches to
enhance adaptive immune responses against pediatric cancer-specific antigenic targets. The proposed Center
will discover and develop effective immunotherapeutic strategies that will be immediat...

## Key facts

- **NIH application ID:** 10401092
- **Project number:** 3U54CA232568-01S2
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Kevin A Cassady
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $173,248
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401092

## Citation

> US National Institutes of Health, RePORTER application 10401092, Engaging and Enhancing Neuroblastoma Immune Targeting (3U54CA232568-01S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401092. Licensed CC0.

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