# Targeting PIM-2 Kinase for Improving Cancer Immunotherapy

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $552,877

## Abstract

Abstract
The adaptive immune system has the capacity to recognize and kill malignant cells. However, immune tolerant
mechanisms that normally protect healthy tissues from autoimmune attack prevent the development of
effective anti-tumor immunity. Tumor uses numerous immunosuppressive mechanisms to evade otherwise
effective T-cell responses. A growing number of immune evasion mechanisms have been characterized
including molecular and cellular mechanisms. Despite promising results achieved by targeting one or more of
these immune evasion mechanisms, there is clearly room for improvement since only a subset of cancer
patients usually respond to such a treatment. The PIM kinases have been studied extensively in tumorigenesis
and as potential therapeutic targets for various cancers. PIM kinases are also expressed on activated T cells,
but their roles in T-cell activity and function are inconclusive and the functions of each isoform in these cells
remain unclear. Using genetically mutant mice, we found that individual PIM kinases play unique as well as
overlapping roles in T-cell response to alloantigens. Strikingly, we consistently observed that PIM-2-deficient T
cells had significantly increased ability to induce graft-versus-host disease (GVHD) after allogeneic bone
marrow transplantation (BMT). More importantly, we found that CD8 T cells mount substantially strong anti-
tumor responses when PIM-2 was deficient or blocked. Our preliminary studies have been extended from
genetic to pharmacologic approaches and from mouse to human T cells. Thus, our preliminary studies provide
compelling evidence that PIM-2 serves as a powerful negative regulator of T-cell immunity against cancer. Our
Central Hypothesis is that targeting PIM-2 substantially promotes cancer immunotherapy while potentially
inhibiting tumor progression directly. This hypothesis will be tested in the following two Specific Aims: 1) To
delineate mechanistic action by which PIM-2 negatively regulates T-cell response; 2) To validate PIM-2 as an
immunotherapy target against cancer. Based on our compelling preliminary data demonstrating for the first
time that PIM-2 negatively regulates T-cell immunity, we expect to firmly validate this observation and to define
the cellular and molecular mechanisms by which this regulation occurs. We also expect to demonstrate that
blockade or inhibition of PIM-2 will enhance anti-tumor immunity against different types of cancer mediated by
both mouse and human T cells.

## Key facts

- **NIH application ID:** 10364948
- **Project number:** 1R01CA258440-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Xue-Zhong Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $552,877
- **Award type:** 1
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364948

## Citation

> US National Institutes of Health, RePORTER application 10364948, Targeting PIM-2 Kinase for Improving Cancer Immunotherapy (1R01CA258440-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10364948. Licensed CC0.

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