# Genetically Modified T cells as Probes and Therapy for Lupus

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $215,499

## Abstract

PROJECT SUMMARY
This is an exploratory project that seeks to investigate the role and potential for therapeutic targeting of CD11c-
expressing cells that include conventional dendritic cells, plasmacytoid dendritic cells, and age-associated B
cells using a switchable chimeric antigen (sCAR) T cell system. This novel strategy differs from the
conventional CAR T cell approach by having a ternary antigen recognition complex instead of the CAR directly
binding the target antigen. Accordingly, target antigen recognition, is mediated by a soluble “switch” Fab, and
therfore, dependence on the switch for sCAR T cell-target cell recognition allows for a controllable system that
can be activated or made quiescent. This is a collaborative project that brings together a PI who has extensive
experience in animal models of lupus and a consortium PI who developed the sCAR T cell system. This
proposal consists of two aims. In aim 1, we will first generate a small library of anti-CD11c switches and then
characterize switches in vitro and in vivo for their ability to promote sCAR T cell activation, survival, and killing
of CD11c cell populations. In aim 2, an anti-CD11c switch will be used in combination with sCAR T cells to
determine if CD11c+ cells are required for maintaining established disease in lupus-prone mice and the effect
of modifying switch dosing schedule on CD11c+ cell numbers and autoimmune disease. This application will
provide new insights into the basic and therapeutic aspects of CD11c-expressing cells in lupus and more
broadly, has the potential for advancing a new powerful methodological approach that: a) will be able to define
the significance of cell populations in normal and disease conditions, b) will be universally and directly
applicable to virtually any mouse model, and c) can be moved to the clinic.

## Key facts

- **NIH application ID:** 9937654
- **Project number:** 5R21AI142137-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DWIGHT H KONO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $215,499
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937654

## Citation

> US National Institutes of Health, RePORTER application 9937654, Genetically Modified T cells as Probes and Therapy for Lupus (5R21AI142137-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9937654. Licensed CC0.

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