# Targeting delivery of mAbs to CNS metastases

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $356,850

## Abstract

It is estimated that around 15% to 40% of cancers spread to the central nervous system (CNS). The treatment
of cancers with brain metastases, however, has been limited by the inefficient deliver of therapeutics to the CNS.
We propose herein a novel strategy, which enables effective delivery of monoclonal antibodies (mAbs), a class
of highly specific and potent protein therapeutics, to the CNS, for the treatment of cancers with brain metastases.
This strategy is based on a nano-encapsulating technology, where mAbs molecules are encapsulated within
nanocapsules of which the surface contains abundant choline and acetylcholine analogues. Such nanocapsules
can be effectively transported across the BBB and deliver the mAbs to the CNS upon systemic administration.
Furthermore, the nanocapsules can be targeted by conjugation with ligands which recognize cell surface markers
on tumor cells. We recently published effective delivery into the CNS of rituximab (anti-CD20) mAbs through
intravenous route using the nanocapsule technology. The nanocapsules were targeted to CXCR5 on the surface
of the tumor cells via conjugation with CXCL13. This therapeutic approach significantly reduced the tumor burden
in the brains of mice xenografted with B-cell lymphomas in comparison with direct native mAbs. In this proposal,
we will further improve the therapeutic efficacy by optimizing the design of the rituximab nanocapsules based on
understanding of the mechanisms of BBB passage and tumor clearance. Success of this project could potentially
enable effective delivery of many other therapeutic mAbs to the CNS, opening a new avenue for treatments of
cancers with CNS metastases.

## Key facts

- **NIH application ID:** 10227048
- **Project number:** 5R01CA253215-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jing Wen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $356,850
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227048

## Citation

> US National Institutes of Health, RePORTER application 10227048, Targeting delivery of mAbs to CNS metastases (5R01CA253215-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227048. Licensed CC0.

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