# Antibody blockade of T cell activating co-inhibitory receptor KLRG1 for treatment of melanoma

> **NIH NIH R43** · ABCURO, INC. · 2020 · $37,385

## Abstract

ABSTRACT
The primary objective of this project is to establish the in vivo therapeutic potential for a new approach to treating
melanoma. Malignant melanoma is a lethal form of skin cancer resulting from the uncontrolled proliferation of
melanocytes. Melanoma is an aggressive malignancy that frequently metastasizes beyond its primary site,
making the disease more difficult to treat. Prognosis following metastasis is grim and median survival, even with
state-of-the-art immunotherapy treatment is less than one year. The current FDA-approved immune checkpoint
inhibitors nivolumab and ipilimumab have produced compelling results, however they are known to cause
significant adverse effects and only produce clinical benefit in a subset of patients. Barriers to advancing safer
and more effective stand-alone or adjuvant immune checkpoint therapies include difficulty identifying appropriate
target molecules with the potency and specificity to mount an immune response against cancer cells without
triggering of tumor escape. Abcuro has identified and characterized a protein cell surface marker for T cells
exhibited in the tumor microenvironment that aligns directly with the degree of T cell differentiation and is highly
exhibited in melanoma-derived tumor infiltrating lymphocytes. We have developed a monoclonal antibody
against this inhibitory receptor which we postulate is capable of precipitating an immune checkpoint blockade on
natural killer and T cells to reactivate effector T cell response against cancer cells. In this proposal we aim to
test whether two lead antibodies against the inhibitory receptor will result in amelioration of tumor pathology in
an animal model relevant to clinical human melanoma. To accomplish this, we will produce and characterize
recombinant humanized antibodies and measure the effect of antibody blockade of the target in a human
peripheral blood cell reconstituted immunodeficient murine melanoma model. In this way we are able to test the
efficacy of antibodies in reducing tumor growth and increasing survival in vivo using human lymphocytes. The
proposed project will establish animal proof of concept for Abcuro’s engineered antibodies in a murine
humanized melanoma model. If successful, we will have produced direct proof-of-concept evidence of the effect
of targeted blockade of this T cell activating co-inhibitory receptor for the treatment of melanoma, allowing us to
further develop our fully characterized lead antibody for clinical trials in human patients.

## Key facts

- **NIH application ID:** 9999546
- **Project number:** 5R43CA243728-02
- **Recipient organization:** ABCURO, INC.
- **Principal Investigator:** Stefano Gulla
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,385
- **Award type:** 5
- **Project period:** 2019-08-20 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999546

## Citation

> US National Institutes of Health, RePORTER application 9999546, Antibody blockade of T cell activating co-inhibitory receptor KLRG1 for treatment of melanoma (5R43CA243728-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999546. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*