# Developing a new bispecific antibody mimicking rapid antigen-specific memory CD8+ T cell-mediated protection

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $210,000

## Abstract

Abstract
While the main function of memory CD8+ T cells is to recognize and kill intracellular pathogens and tumors,
they can also produce multiple effector cytokines and chemokines that contribute to protective immune
responses. The precise mechanism for development of memory CD8+ T cell protection in vaccinated hosts is
not well understood. We have been investigating this question over the past 15 years with the underlying goal
to develop novel therapeutic strategies that harness the power of memory CD8+ T cells to the benefit of the
host. Our past and most recent mechanistic studies have established that, upon recall infection of vaccinated
hosts, memory CD8+ T cells can rapidly sense both inflammatory signals and cognate antigen to produce
interferon gamma (IFNγ) and sets of early coordinated chemokines. We reported that both signals are required
to promote potent activation of inflammatory Ly6C+ monocytes microbicidal effector function and achieve
optimal protection of vaccinated hosts. Building on these results, we propose in this exploratory proposal to
design, develop and test a novel bispecific IFNγ-chemokine Fc-fusion “ligand-trap” biologics that target and
activates Ly6C+ monocytes microbicidal functions for protection against infectious diseases, mimicking the
mechanism by which memory CD8+ T cells mediate effective protection of vaccinated host during recall
infection. We believe that such reagent has the potential to be used as a rapid and broad therapeutic against
multiple acute infections.

## Key facts

- **NIH application ID:** 10852950
- **Project number:** 5R21AI167363-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Jonathan R. Lai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,000
- **Award type:** 5
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852950

## Citation

> US National Institutes of Health, RePORTER application 10852950, Developing a new bispecific antibody mimicking rapid antigen-specific memory CD8+ T cell-mediated protection (5R21AI167363-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10852950. Licensed CC0.

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