# Personalized, antigen-directed immunotherapy delivered to lymph nodes

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $548,896

## Abstract

Project Summary
T-cell priming is orchestrated in the sequestered environment of lymph nodes (LNs) where a cascade of co-
inhibitory and co-stimulatory signals from an assembly of cell types determines systemic, immunodominant
responses to regionally presented antigens (Ag). Yet tumor draining LNs (tdLNs) are often tolerized against
tumor Ags (tAgs), rendering an otherwise inhospitable environment permissive to regional LN metastases and
eventual dissemination throughout the body. While checkpoint blockade immunotherapy (CBI) cancer therapy
is meant to re-invigorate T-cell priming and effector function against tAgs, these therapies are administered i.v.
without regard to all the other non-tAgs that are present in the body. As a result of this Ag-indiscriminate
activity, CBI can cause immune related adverse events (irAEs) that limit the use of current and emerging CBI.
In addition, because tdLNs are already tolerized to tAgs by the time of cancer detection, the effectiveness of
CBI to potently prime tAg-specific T-cell responses may be limited. While CBI does result in durable cancer
cures, most cancer types are non-responsive and the majority of patients with cancers known to be responsive
either do not benefit from CBI treatment or experience relapse and irAEs.
In this application, multi-disciplinary teams from the University of Texas and University of Bern collaborate to
deliver both tAg and CBI to non-tdLNs in order to mount efficient, tAg-directed CBI without the irAEs that
impact other CBI combinational therapies. Specifically, the team proposes to develop and use a translatable,
plant-based, virus-like-particle (VLP) platform presenting private tumor neoantigens (tNeoAgs) and to combine
it with CBI delivered to lymphatic watersheds in syngeneic mouse models of triple negative breast cancer
(TNBC). Effectiveness of the approach is evidenced by strong preliminary data showing enhanced anti-tumor
responses accompanied by clonal expansion of cytolytic, tAg-specific tumor infiltrating lymphocytes from
bioinformatic analyses of single cell RNA sequencing. The team further proposes to separately dose different
VLP-tNeoAgs with CBI to discrete lymphatic watersheds to mount multiple, immunodominant responses to
combat tumor immune escape and regrowth. The team will also test safety of the approach in a transgenic
mouse susceptible to induced lymphatic infiltration in normal tissues as a clinical readout of irAEs following CBI
dosing. Because the teams have translated their respective technologies into clinical studies, the
developments made herein could be rapidly implemented to improve the efficacy of current and emerging CBI,
establish the concept of personalized cancer vaccines, and expand the use of CBI in TNBC patients who have
limited treatment options.

## Key facts

- **NIH application ID:** 10874554
- **Project number:** 5R01CA276513-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Mona Mohsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $548,896
- **Award type:** 5
- **Project period:** 2023-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874554

## Citation

> US National Institutes of Health, RePORTER application 10874554, Personalized, antigen-directed immunotherapy delivered to lymph nodes (5R01CA276513-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10874554. Licensed CC0.

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