# Characterizing ALCAM as an oncoprotein and immunotherapeutic target in neuroblastoma

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $45,520

## Abstract

Project Summary
Neuroblastoma is a pediatric extracranial solid malignancy that arises from the developing sympathetic nervous
system. Patients with high risk neuroblastoma face five-year survival rates of only 50%, despite intensive
intervention with chemotherapy, surgery, radiation, and immunotherapy. Development of new therapies for
neuroblastoma has been challenging due to the paucity of targetable oncogenic mutations. However, recent
approval of monoclonal antibody therapy targeting GD2 has credentialed immunotherapy as a new avenue of
therapeutic development in neuroblastoma. Conversely anti-GD2 therapy causes significant on-target, off-tumor
toxicity due to the presence of GD2 on nociceptive neurons, and relapse due to loss of GD2 expression remains
common. To subvert antigen downregulation as a mechanism of resistance, our lab focuses on development of
immunotherapy targets that are both differentially expressed and necessary for tumor survival. We recently
identified the cell adhesion molecule ALCAM as a potential target for immunotherapy development. ALCAM is a
cellular adhesion molecule involved in retinal ganglion development, and high ALCAM expression is a negative
prognostic marker in a variety of cancers. Our RNA-sequencing data shows ALCAM is highly expressed in most
patient neuroblastomas. Furthermore, an ALCAM-targeted antibody-drug conjugate, CX-2009, is currently in
clinical trials for advanced metastatic or locally unresectable adult cancers. This project aims to discover the
mechanism of ALCAM overexpression in neuroblastoma, as well as define the contribution of ALCAM
overexpression to tumor growth and metastasis. Preliminary data suggests shRNA-mediated ALCAM
knockdown induces neurite formation in vitro, a phenotype associated with differentiation. Additionally, ChIP-
sequencing data from two neuroblastoma cell lines shows expression ALCAM may be regulated by a network of
transcription factors termed the core regulatory circuit (CRC). The CRC is a feed-forward transcriptional
regulatory circuit in which each transcription factor regulates the expression of itself and the others, together
defining a noradrenergic phenotype characterized by expression of proteins such as tyrosine hydroxylase and
dopamine beta hydroxylase. By integrating bioinformatics and molecular biology approaches, we will uncover
the mechanism of ALCAM overexpression in neuroblastoma. More broadly, this project will credential ALCAM
as a viable target of immunotherapy, as well as an oncoprotein necessary for tumor survival.

## Key facts

- **NIH application ID:** 10067673
- **Project number:** 1F31CA254244-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jarrett Lindsay
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 1
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067673

## Citation

> US National Institutes of Health, RePORTER application 10067673, Characterizing ALCAM as an oncoprotein and immunotherapeutic target in neuroblastoma (1F31CA254244-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067673. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*