# RBC-mediated mopping of cytokines for the treatment of pneumonia

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $243,750

## Abstract

ABSTRACT / SUMMARY
 Despite the advent of antibiotics and antivirals, pneumonia remains a major killer. In typical years, it
kills >50,000 Americans, and in the last year, nearly 10x that amount due to COVID-19. The reason for these
deaths is rarely because we cannot stop microbial expansion. Rather, it is due to the host response, in which
local inflammation in the lungs causes a very high concentration of pro-inflammatory cytokines to spill into the
blood, whereupon the cytokines travel to and damage remote organs.
 To eliminate excessive cytokines, many antibodies have been developed to bind and neutralize
cytokines. However, these antibodies extravasate into the infected tissue (lungs), where they also inhibit the
beneficial function of these cytokines, which is the orchestration of leukocytes to clear the microbes. To
prevent this problem and the subsequent microbial overgrowth, there is a need to engineer therapeutics that
only quench cytokines in the bloodstream, and not in the infected tissues that rely upon cytokines for microbial
clearance.
 To accomplish this, we have developed RBC-Mops. RBC-Mops bind and quench cytokines, but only in
the bloodstream, with no extravasation into infected tissues. We will build and test RBC-Mops across two
Aims: In Aim 1, we will test RBC-Mops ability to bind their targets in vitro, evaluate for damage to RBCs
themselves, and determine the pharmacokinetics and biodistribution of RBC-Mops in naive mice. In Aim 1, we
will test RBC-Mops in the Klebsiella mouse model of pneumonia, evaluating benefits to the lungs and remote
organs, while also investigating potential side effects.
 This R21 is designed to produce and validate the prototype RBC-Mop within 2 years. After that, we will
apply for an R01 to further the translational potential of RBC-Mops and better understand their mechanisms.
Eventually, we hope to develop a combination of RBC-Mops that can eliminate cytokines and other circulating
toxins, to ameliorate a large range of acute illnesses, including viral pneumonia (COVID-19), sepsis, and sterile
cytokine release syndromes produced by immunological therapies.

## Key facts

- **NIH application ID:** 10495259
- **Project number:** 5R21AI166778-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jacob Brenner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,750
- **Award type:** 5
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495259

## Citation

> US National Institutes of Health, RePORTER application 10495259, RBC-mediated mopping of cytokines for the treatment of pneumonia (5R21AI166778-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10495259. Licensed CC0.

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