Delving into the Latest Updates on KYK-2.0 IgG1 (NCI) with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms-

Target

ULBP1

Mechanism

ULBP1 modulators(UL16 binding protein 1 modulators)

Therapeutic Areas

NeoplasmsImmune System DiseasesInfectious Diseases+ [1]

Active Indication-

Inactive Indication

Autoimmune DiseasesDisorder related to transplantationInfectious Diseases+ [1]

Originator Organization

National Cancer Institute

Active Organization-

Inactive Organization

National Institutes of Health

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

In humans, NKG2D is an activating receptor on natural killer (NK) cells and a costimulatory receptor on certain T cells and plays a central role in mediating immune responses in autoimmune diseases, infectious diseases, and cancer. Monoclonal antibodies that antagonize or agonize immune responses mediated by human NKG2D are considered to be of broad and potent therapeutic utility. Nonetheless, monoclonal antibodies to NKG2D that are suitable for clinical investigations have not been published yet. Here, we describe the generation, affinity maturation, and characterization of a fully human monoclonal antibody to human NKG2D. Using phage display technology based on a newly generated naïve human Fab library in phage display vector pC3C followed by a tandem chain shuffling process designed for minimal deviation from natural human antibody sequences, we selected a human Fab, designated KYK-2.0, with high specificity and affinity to human NKG2D. KYK-2.0 Fab blocked the binding of the natural human NKG2D ligands MICA, MICB, and ULBP2 as potently as a commercially available mouse anti-human NKG2D monoclonal antibody in immunoglobulin G (IgG) format. Conversion of KYK-2.0 Fab to IgG1 resulted in subnanomolar avidity for human NKG2D. KYK-2.0 IgG1 was found to selectively recognize defined subpopulations of human lymphocytes known to express NKG2D, that is, the majority of human CD8+, CD16+, and CD56+ cells as well as a small fraction of human CD4+ cells. In solution, KYK-2.0 IgG1 interfered with the cytolytic activity of ex vivo expanded human NK cells. By contrast, immobilized KYK-2.0 IgG1 was found to strongly induce human NK cell activation. The dual antagonistic and agonistic activity promises a wide range of therapeutic applications for KYK-2.0 IgG1 and its derivatives.

100 Deals associated with KYK-2.0 IgG1 (NCI)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Autoimmune Diseases	Discovery	US	National Institutes of Health	-
Disorder related to transplantation	Discovery	US	National Institutes of Health	-
Infectious Diseases	Discovery	US	National Institutes of Health	-
Neoplasms	Discovery	US	National Institutes of Health	-