# Engager T cell: A Simple Solution for Off-the-shelf T Cell Therapy for Cancer

> **NIH NIH R43** · IMMUNEBRO THERAPEUTICS INC. · 2024 · $361,635

## Abstract

Project Summary
Autologous chimeric antigen receptor T (CAR T) cell therapy poses logistical and economical
challenges despite curative potential. Donor-derived allogeneic off-the-shelf (OTS) cell therapies
have become the holy grail of cell therapy as they can be mass-produced and are immediately
available to cancer patients at affordable prices. However, current OTS strategies involve
complex manufacturing process and gene-editing with safety concerns such as carcinogenesis
risk. Non-αβ T cell-based OTS strategies such as NK cells have potency concerns as they lack
persistence and durability. Immunebro Therapeutics is developing a simple and novel
platform technology to produce donor-derived αβ T cell-based OTS products named
engager T cells. Engager T cells are engineered donor T cells expressing and secreting an
artificial modular protein that can 1) target donor T cells to a desired cancer target and 2) curb
donor T cells' alloreactivity of inducing graft versus host disease (GvHD). Donor derived engager
T cell is a simple solution for OTS T cell therapy with no need of gene editing. It involves
a well-established and much less complex manufacturing process in comparison to gene
edited OTS CAR T cells currently in development. Preliminary data have demonstrated that
donor derived CD19-targeting engager T cells have low xenogeneic GvHD risk and are efficacious
in treating xenograft CD19+ leukemia mouse model. However, in a side-by-side comparison,
CD19 engager T cells are inferior to 2nd gen CD19 CAR T cells on efficacy due to the lack of co-
stimulation. As efficacy is crucial for regulatory and commercial success of any drug candidates,
this proposal is aiming at developing enhanced CD19 engager T cells with low GvHD risk.
Specific Aim 1 is to develop enhanced CD19 engager T cells and assess transgene expression
and secretion. Three strategies will be used to produce enhance CD19 engager T cells by 1) co-
expressing a CD19 CAR; 2) co-expressing T cell promoting cytokine IL15; 3) co-expressing
costimulatory factor 4-1BBL and CD80. Specific Aim 2 is to demonstrate one or more of the
enhanced CD19 engager T cells have low xenogeneic GvHD risk in immune deficient mice.
Specific Aim 3 is to demonstrate one or more of enhanced CD19 engager T cells have
comparable efficacy to 2nd gen CD19 CAR T cells. By the end of Phase 1 work, Immunebro will
have enhanced CD19 engager T cells as the first product prototype built from the simple and
novel OTS platform. This platform can be used to build a rich pipeline of OTS T cells
targeting a variety of cancers with less complex manufacturing, safer profile, and
comparable or better efficacy than gene edited OTS CAR T cells currently in development.

## Key facts

- **NIH application ID:** 10820780
- **Project number:** 1R43CA281523-01A1
- **Recipient organization:** IMMUNEBRO THERAPEUTICS INC.
- **Principal Investigator:** GONGBO LI
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $361,635
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820780

## Citation

> US National Institutes of Health, RePORTER application 10820780, Engager T cell: A Simple Solution for Off-the-shelf T Cell Therapy for Cancer (1R43CA281523-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10820780. Licensed CC0.

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