# Identification and cloning of neoantigen-specific T cells for GBM immunotherapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $402,457

## Abstract

SUMMARY/ABSTRACT
The lack of effective glioblastoma treatments poses a significant health problem and highlights the need for novel
and innovative approaches. Immunotherapy is an appealing strategy because of the potential ability for immune
cells to traffic to and destroy infiltrating tumor cells in the brain. New information suggests that patients mounting
immune responses after immunotherapy preferentially recognize novel neoantigens created by tumor-specific
mutations. Our data, and that from other immunotherapeutic strategies for patients with cancer, suggest that
the vast majority of tumor-specific T cells induced by such personalized, patient-specific immunotherapies
do NOT recognize well-characterized, known antigens. Such information is consistent with recent data from
other immune-responsive cancers, such as melanoma, in which the percentage of tumor-specific T cells
recognizing known antigens was less than 1%. In order to design the most effective immunotherapeutic
strategies for glioblastoma, we believe that it is critical to understand which antigens tumor-specific T cells
recognize in this disease. Our hypothesis is that glioblastoma patients treated with immunotherapy will
mount anti-tumor immune responses against specific mutations and splice variants in their individual
tumors. Similarly, our other recent findings strongly suggest that the addition of PD-1 antibody (mAb) blockade
to DCVax enhances both the intra-tumoral CD8+ T cell response and clinical benefit in pre-clinical studies.
Furthermore, the timing of PD-1 mAb blockade is immunologically relevant; our unpublished, recent clinical trial
results highlight how the neoadjuvant (prior to surgery) treatment with PD-1 mAb blockade induces enhanced
anti-tumor immune responses and clinical benefit. We hypothesize that the addition of PD-1 mAb blockade
should amplify the neoantigen-specific T cell response induced by DC vaccination, both in the blood
and the tumor. To test these important questions, In Aim 1, we will develop a new bioinformatics pipeline to
predict neoantigens that arise specifically from the types of genetic alterations that occur in GBM. In Aim 2, will
create immunocompetent murine glioma models to test the importance of neoantigens. Finally, in Aim 3, we will
identify neoantigen-specific T cells from both the TIL population and peripheral blood of GBM patients treated
with immunotherapy. These studies span the continuum of translational research in brain tumor immunotherapy
and will likely provide informative new insights for the development of new, rational immune-based strategies for
brain tumor patients.

## Key facts

- **NIH application ID:** 10375387
- **Project number:** 5R01CA222695-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Robert M Prins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,457
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375387

## Citation

> US National Institutes of Health, RePORTER application 10375387, Identification and cloning of neoantigen-specific T cells for GBM immunotherapy (5R01CA222695-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375387. Licensed CC0.

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