# Examining the impact of endogenous CD28 signaling on CAR T cells

> **NIH NIH R03** · ROSWELL PARK CANCER INSTITUTE CORP · 2022 · $84,100

## Abstract

Project Abstract/Summary.
Recent advances in immune cell engineering have revolutionized the treatment of blood cancers. Genetic
modification of T cells, whose physiological job is to kill infected and mutant cells throughout our bodies, with
Chimeric Antigen Receptors (CARs) can redirect T cell killing activity against malignant cells that express certain
target proteins on their surface. CARs are built to mimic physiological T cell signaling, which is unique in its
requirement for two signals provided by the T cell receptor (TCR) and co-receptors, such as CD28, to induce T
cell function. Recent clinical studies in multiple myeloma (MM), a common incurable blood cancer, have shown
that CAR T cells are remarkably effective at treating patients who do not respond to standard of care
chemotherapies. Despite this, most MM patients relapsed within a year of CAR T cell therapy and the cause of
their relapses was not readily apparent. The long-term goal of the project proposed in this grant application is to
use our knowledge or T cell signaling to make CAR T cell therapy for MM more effective. To this end, we have
found that endogenous CD28 on CAR T cells disrupts their ability to kill MM cells that express CD28 stimulatory
proteins CD80 and CD86. However, the same endogenous CD28 is essential for making CAR T cells and we
have also found that the CD28 signal provided during the CAR T cell manufacturing process helps determine
how good of tumor killers CAR T cells become. Proposed studies seek to 1) identify ways to manipulate CD28
signaling during CAR T cell manufacture that can improve their long-term ability to kill MM cells in patients, and
2) determine how endogenous CD28 signaling causes dysfunction of CAR T cells. Results of these studies will
have direct clinical implications because adjustments to the CAR T cell manufacturing process could be rapidly
implemented and a drug that blocks CD28 activation, abatacept, is already used to treat people suffering from
rheumatoid arthritis.

## Key facts

- **NIH application ID:** 10318192
- **Project number:** 5R03CA256122-02
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Scott Henry Olejniczak
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $84,100
- **Award type:** 5
- **Project period:** 2020-12-11 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318192

## Citation

> US National Institutes of Health, RePORTER application 10318192, Examining the impact of endogenous CD28 signaling on CAR T cells (5R03CA256122-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10318192. Licensed CC0.

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