# Effective Anti-Tumor Vaccination - Targeting Checkpoint Regulation at the Time of T-cell Activation

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $349,988

## Abstract

Prostate cancer is a significant global health concern for which new treatments are needed. The long-range goal
of our research for nearly two decades has been to develop active immunotherapies, and tumor vaccines in
particular, as treatments for prostate cancer. We have focused on DNA vaccines as a simple method, and one
specifically aimed at generating tumor antigen-specific CD8 T cells. A major effort in our laboratory over the last
several years has been to evaluate the tumor response to immunization and identify mechanisms of resistance
to immunization. We have found that PD-1 or LAG-3 are upregulated after T cell activation with vaccination, and
that even the transient expression of PD-1 or LAG-3 following antigen-specific T-cell activation is sufficient to
allow them to be regulated in the immunosuppressive tumor environment, and this can be abrogated using
concurrent blockade of PD-1 or LAG-3. We have recently demonstrated that this is true in humans as well, as
delivery of a PD-1 blocking antibody (pembrolizumab) at the time of immunization with a DNA vaccine, rather
than beginning weeks after immunization, elicited objective anti-prostate tumor responses. This forms the basis
of the hypothesis underlying this proposal, namely that given the dynamic nature of the expression of PD-1 or
LAG-3 following anti-tumor immunization, blockade of the transient upregulation of regulatory T cell markers
(including PD-1 and/or LAG-3) using either antibody blockade or using TLR agonists that reduce expression of
these regulatory receptors at the time of T-cell activation via anti-tumor immunization will lead to greater effector
CD8 T cells and greater anti-tumor efficacy.

## Key facts

- **NIH application ID:** 10151566
- **Project number:** 5R01CA219154-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** DOUGLAS G. MCNEEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,988
- **Award type:** 5
- **Project period:** 2017-06-09 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151566

## Citation

> US National Institutes of Health, RePORTER application 10151566, Effective Anti-Tumor Vaccination - Targeting Checkpoint Regulation at the Time of T-cell Activation (5R01CA219154-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10151566. Licensed CC0.

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