# Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $347,078

## Abstract

Neuroblastoma is the most common extracranial solid tumor seen in children, and expresses the
disialoganglioside GD2 on its surface. For patients who have high risk disease or whose disease recurs after
completing therapy, there are limited options. Allogeneic hematopoietic stem cell transplant (AlloHSCT) is a
transfusion of hematopoietic stem cells from a healthy donor to a patient who has been treated with high doses
of chemotherapy and/or radiation, and is typically used clinically for children with leukemia or lymphoma. But
alloHSCT has had limited success thus far in attacking neuroblastoma with a graft-versus-tumor (GVT) effect,
and has introduced lethal graft-versus-host-disease (GVHD). The long term objective of this proposal is to
enhance the GVT effect against neuroblastoma. This proposal explores 3 specific aims to improve GVT effects
using animal models of alloHSCT. First we will explore usage of an immunocytokine called hu14.18-IL2, a
humanized GD2 monoclonal antibody linked to interleukin (IL)-2, to enhance the GVT effect, improving the
efficacy of the transplant. This antibody has already been given to children with neuroblastoma in clinical trials
but is not curative, and has not been tested in the alloHSCT setting. Second, we will activate allogeneic natural
killer (NK) cells with IL-15 and CD137L-expressing artificial antigen presenting cells, and infuse them for the
first time with hu14.18-IL2 as a combination strategy for improving GVT further. We will control any potential
GVHD by inhibiting the JAK/STAT pathway and blocking tumor necrosis factor-alpha production. Lastly, we will
label NK cells with a nonradioactive isotope of fluorine (¹⁹F) that will make these cells detectable by MRI,
determine how ¹⁹F-labeled NK cells traffic to neuroblastoma tumors after alloHSCT and if hu14.18-IL2 can
further attract NK cells to the tumor. The ultimate goal is to support the research priorities of the National
Cancer Institute by developing research that will lead to novel therapies for neuroblastoma. Success of any of
the individual aims will be a major advance in making alloHSCT more effective for neuroblastoma. Successful
translation of the entire proposal will lead to an innovative combination immunotherapy platform for treating
neuroblastoma.

## Key facts

- **NIH application ID:** 10403986
- **Project number:** 5R01CA215461-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Christian Capitini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $347,078
- **Award type:** 5
- **Project period:** 2018-07-03 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403986

## Citation

> US National Institutes of Health, RePORTER application 10403986, Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma (5R01CA215461-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10403986. Licensed CC0.

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