# Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $176,000

## Abstract

PROJECT SUMMARY
A solid Consortium project should contribute a unique and compelling approach to neuroblastoma
and supply tools or components that enable other members of the Consortium to make their best
work even better. The project detailed here commences with the selection and careful
characterization of a dozen fully human antibodies to Glypican-2, the most promising antigen in
neuroblastoma, from a pre-existing hybridoma stock. These antibodies, along with their full
sequences, binding affinities, cellular internalization, epitope, and (where possible) crystal structures,
will be made available to Consortium members within the first year for use in their modality of choice.
This project will explore their utility as components in double bispecific antibody therapy: this double
bispecific approach targets two cancer antigens and two T cell receptors simultaneously, inducing T
cell activation and co-activation only in the presence of cancer cells expressing both antigens. The
double targeting strategy should allow for a much higher level of selective engagement and killing
than has heretofore been possible with therapies that target only a single cancer antigen, and should
it prove effective in neuroblastoma the approach is likely to have utility in a wide variety of cancers.
One historical weakness for the development of immuno-oncology approaches such as this one is
that the animal models have had very little predictive value. For this reason, the best of the
humanized mouse models, “MISTRG” mice, will be used both for the development of these molecules
and for testing the other consortium members’ approaches, where they could be useful. CIVO multi-
needle array technology will be employed to simplify the combinatorial challenge associated with
testing pairs of bispecific molecules; this technology will also be open for use collaboratively with the
other Consortium members. In short, the proposal provides the Consortium with human antibodies
against a validated neuroblastoma target, access to the current state-of-the-art in humanized mice, a
CIVO multi-needle array device to facilitate testing therapeutics, and a double bispecific antibody
therapeutic approach that promises a high level of T cell killing and selectivity and a likely broad
applicability beyond neuroblastoma.

## Key facts

- **NIH application ID:** 10228852
- **Project number:** 3U01CA232490-01S1
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** JAMES M OLSON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,000
- **Award type:** 3
- **Project period:** 2018-09-10 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228852

## Citation

> US National Institutes of Health, RePORTER application 10228852, Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma (3U01CA232490-01S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10228852. Licensed CC0.

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