Recombinant ILT3 protein-produced antibodies for immunotherapy treatment of cancer

This technology is a recombinant protein-induced antibody collection against Immunoglobulin-Like Transcript 3 (ILT3) that can modulate cancer cell growth and induce immune checkpoint blockade.

Unmet Need: Precise immunotherapies for treating cancer

A major limitation to current treatment options for cancer are the associated detrimental side effects that occur because of the broad expression profile of the therapeutic target. Consequently, many chemotherapies are recognized to be cytotoxic, have poor tolerance, and low efficacy as a first line therapy. Immunotherapies, which seek to elicit a targeted immune response against specific disease markers, provide a promising method to improve the safety and specificity of chemotherapies. However, the lack of basic scientific knowledge surrounding many immunological proteins and their ligands precludes their use as immunotherapies.

The Technology: Recombinant ILT3 protein-derived antibodies for treatment of cancer

This technology encompasses a collection of antibodies against ILT3, an innate immune receptor expressed in normal and malignant cells, that has been shown to act directly on myeloid malignancies and induce immune checkpoint blockade. The recombinant protein, ILT3.Fc, used to generate these antibodies has previously been studied as a therapeutic for autoimmune disease due to ILT3’s role in immunologic quiescence through modulation of T-cell activity. Until now, production of therapeutic antibodies has remained limited. Dr. Suciu-Foca and her team have developed antibodies, two agonistic and one antagonistic, to ILT3 using the recombinant protein ILT3.Fc. ILT3.Fc has been shown to bind activated and non-resting T cells to alter activity and directly affect tumor growth. In vitro and in vivo studies have shown a dose-dependent interaction between ILT3.Fc and CD166 and provided mechanistic information on the anti-tumor properties. As such, these antibodies provide therapeutic and diagnostic potential for cancer immunotherapy treatment, and act directly on ILT3 positive myeloid malignancies.

ILT3.Fc has been used to produce three anti-ILT3 antibodies from mice, which are demonstrated to bind membrane-bound ILT3 in an advanced chronic lymphocytic leukemia with lymph node involvement and acute myeloid leukemia with monocytic differentiation.

Applications:

• Immunotherapy for the treatment of cancer
• Diagnostic tool for cancer
• Treatment of autoimmune diseases
• Immunosuppressive treatment of allograft recipients
• Research tool for analysis of effects of antibody therapy on cell signaling

Advantages:

• Highly specific interaction with CD166-expressing cells
• Is available in multiple antibody formulations both as an inhibitor and activator of downstream signaling
• Arrests cancer cell growth both in vitro and in vivo
• Acts directly on ILT3-positive myeloid malignancies
• Fewer side effects and lower toxicity
• Can be combined with other chemotherapeutic agents

Lead Inventor:

[Nicole Suciu-Foca, Ph.D.]

Patent Information:

Patent Issued

Related Publications:

• Xu Z, Lin CC, Ho S, Vlad G, Suciu-Foca N. “Suppression of Experimental Autoimmune Encephalomyelitis by ILT3. Fc” The Journal of Immunology. 2021 Feb 1; 206(3): 554-565.

• Xu Z, Chang CC, Li M, Zhang QY, Vasilescu EM, D’Agati V, Floratos A, Vlad G, Suciu-Foca N. “ILT3.Fc-CD166 Interaction Induces Inactivation of p70 S6 Kinase and Inhibits Tumor Cell Growth” J Immunol. 2017 Dec; pii: ji1700553.

• Vlad G, Suciu-Foca N. “Induction of antigen-specific human T suppressor cells by membrane and soluble ILT3” Exp Mol Path. 2012 Dec; 93(3): 294-301.

Tech Ventures Reference:

• CU15207, CU17285

• Licensing Contact: Devin Jones