Active project

Yael Mossé, MD

Children’s Hospital of Philadelphia

Translation of an ALK-directed Antibody Drug Conjugate for Neuroblastoma

Dr. Mossé’s team is developing an antibody-drug conjugate that targets ALK, a protein found on many neuroblastoma cells. The project is refining the therapy, assessing its safety and effectiveness in the laboratory, and identifying a lead candidate for future clinical development.

CureSearch Acceleration Initiative Award

2025–2028 · Neuroblastoma

Project Overview About the Researcher Research Updates

Children diagnosed with advanced solid tumors face serious challenges: fewer than half survive, and those who do often endure lasting and sometimes life-threatening side effects. Neuroblastoma, the most common extracranial solid tumor in children, affects approximately 700 children in the US each year. Nearly half of these cases are classified as high-risk, a prognosis with an overall survival rate of less than 50%.

Dr. Yael Mossé, a CureSearch Acceleration Initiative awardee at the Children’s Hospital of Philadelphia, is working to improve these odds by developing a novel immunotherapy for high-risk neuroblastoma patients. While immunotherapies have achieved remarkable success in treating blood cancers, their progress in solid tumors has been limited. This is largely due to the challenge of identifying targets found on cancer cells but not on healthy tissue.

Dr. Mossé’s research focuses on one such promising target: Anaplastic Lymphoma Kinase (ALK), a protein expressed on the surface of neuroblastoma cells but absent from normal cells. ALK is found in other pediatric cancers as well, including subsets of rhabdomyosarcoma and Ewing sarcoma, in addition to several adult cancers, making it a compelling target for immunotherapy.

To target ALK, Dr. Mossé and her team are developing an ALK-directed antibody-drug conjugate (ADC). ADCs are a rapidly emerging class of drugs that combine an antibody that recognizes a specific protein on cancer cells, such as ALK, with a powerful cancer-fighting drug. This approach enables precise delivery of the drug to the cancer cells, sparing healthy tissue. Their first-generation ALK-directed ADC has shown strong and sustained tumor shrinkage in preclinical models. With CureSearch funding, Dr. Mossé will refine this therapy and assess its safety and efficacy in the lab. These efforts are designed to identify a lead candidate for clinical development and pave the way for a future clinical trial in children with high-risk neuroblastoma, bringing a potentially curative treatment to currently incurable patients.

This project is supported in part by the Norcross Foundation.

Project at a glance

Program: Acceleration Initiative Award
Institution: Children’s Hospital of Philadelphia
Focus: Neuroblastoma

Yael Mossé, MD

Dr. Yael Mossé is a physician-scientist at Children’s Hospital Philadelphia who has spent over two decades advancing research and treatment for neuroblastoma.

She led the discovery of ALK mutations as key drivers of the disease and has translated this work into targeted therapies, including FDA-approved ALK inhibitors. Her lab continues to develop novel approaches-including immunotherapy and protein degradation strategies-to overcome resistance and target additional drivers like MYCN, ATRX, and RAS, with the ultimate goal of improving outcomes for children with high-risk cancers.

Who is Yael Mossé, MD? Dr. Yael Mossé is an attending physician at the Children’s Hospital of Philadelphia and a Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, where she also hods the Patricia Brophy Endowed Chair in Neuroblastoma Research. As a physician-scientist, Dr Mossé has dedicated her career to advancing the treatment for neuroblastoma – both by improving outcomes for patients and by using the disease as a model to better understand how cancers develop. She is the recipient of the 2025 CureSearch Acceleration Initiative Award for her project, “Translation of an ALK-directed Antibody Drug Conjugate for Neuroblastoma.”

Follow the project’s progress.

Research Update — June 2026

Dr. Mossé and her team continue to make strong progress toward developing a first-in-class ALK-directed ADC for children with neuroblastoma and other ALK-expressing cancers.

Since the start of the award, the team has engineered and tested multiple versions of the ADC, pairing their ALK-targeting antibody with different cancer-killing payloads to identify the most promising candidate for clinical development. Laboratory studies across a panel of neuroblastoma cell lines demonstrated potent anti-tumor activity that was directly linked to the amount of ALK present on the surface of cancer cells, providing important insight into which patients may be most likely to benefit from this targeted therapy.

Building on these findings, the team completed initial studies in mouse models of neuroblastoma and observed significant tumor shrinkage with their leading ADC candidates. Additional studies are now underway to optimize drug loading, evaluate how the therapy distributes throughout the body, and further refine dosing strategies. Importantly, the team continues to collaborate with a manufacturing partner to support the development and future production of a clinical-grade version of the therapy. Together, these accomplishments represent important milestones toward filing a regulatory application and launching a first-in-human clinical trial for children with neuroblastoma and other ALK-driven cancers.