GEAR-NK
GEAR-NK is our allogeneic NK cell therapy that have been Genetically Engineered for Antibody Resistance (G.E.A.R.). Our approach provides NK cell therapies with “precision shielding” that protects them from being targeted and destroyed by commonly used antibody therapeutics. Why is this important? Find out below.
GEAR-NK: Scientific Foundations
Background: mAbs Rely On NK Cells
When a therapeutic monoclonal antibody (mAb) is administered, NK cells inside the patient’s body cooperate with it to eliminate target cells through antibody-dependent cellular cytotoxicity (ADCC). This refers to when NK cells target and kill antibody-coated cells, and it is actually one of the main ways that mAbs exert their therapeutic activity.
The Problem: mAb-Mediated Fratricide
NK cells express some of the same surface molecules that are targeted by prominent mAbs, particularly those used to treat certain hematological conditions, such as CD38. These mAbs coat NK cells inside the body, causing them to target and kill each other; a phenomenon known as “fratricide”. This results in a sort of self-destruction, with the mAb eliminating the very cells it relies on for its activity.
Gen. I Approach: Delete the mAb Target From NK Cells
A potential “solution” to this conundrum would be to deploy NK cells that have had the target molecule deleted – combining a CD38 mAb with CD38-KO NK cells, for example – making them “resistant to fratricide”. While this makes sense in theory, there is an issue: many of these surface molecules, especially CD38, are integral to NK cell activity, so their deletion hinders effector function.
Our Novel Solution: GEAR-NK Cells
We have developed an effective solution to this problem. Instead of deleting the surface marker, we MODIFY it. Specifically, through rigorous assessment of protein structure data, we identify crucial amino acids involved in mAb binding. Then, using CRISPR-based genetic editing techniques, we “gently” edit the target molecule, such as CD38, altering the structure just enough to disrupt mAb binding, while retaining full enzymatic function.
Here’s how we do it.
Precision Shielding
At GEAR, we don’t delete the target protein. Instead, we modify it in a highly precise manner that disrupts the mAb binding epitope while retaining full enzymatic function.
Protein Structure & Epitope Analysis
First, we will rigorously analyze the biochemical structure of the target molecule to identify potential sites of mAb binding. Typically, several amino acids are identified as "potentially critical" and are subsequently mutated - creating several single-mutant variants of the original molecule.
Testing to Ensure Precision Shielding
Once the mutants are made, we will express them into relevant cell types and test for three things: 1. Is the target molecule is still expressed on the surface? 2. Is is unable to be bound by the mAb in question?. 3. Does the mutant-expressing NK cell still function completely normally? If the answer to all three of these is "yes", we move forward.
GEAR-NK Cells
The final product is a brilliantly crafted NK cell therapy that is finely tuned to augment the therapeutic activity of a very specific mAb, perfect for combination therapies.
OUR CELL SOURCE
Pooled Donor UCB-Derived Stem Cells
We use umbilical cord blood (UCB)-derived CD34+ hematopoietic stem cells that are then differentiated into NK cells as the starting material for our GEAR-NK cells.
what makes UCB-Derived Stem Cells Superior?
UCB Stem Cells are YOUNG!
UCB-derived stem cells are very young (they have short telomeres) and, so allow for the subsequent immune cell therapy to proliferate at very high levels for a prolonged period of time.
UCB Stem Cells are HEALTHY!
These cells have been being nurtured in a very protected environment before we gain access to them. So, they are relatively clean of cellular damage and viral infection that would otherwise compromise cell therapy efficacy.
UCB Stem Cells are ABUNDANT!
Umbilical cord blood is often considered medical waste due to its limited applications in traditional medicine. However, this abundance makes it an easily accessible resource for stem cell therapy and research, as it is typically discarded after birth unless specifically collected.
GEAR Therapeutics'
In-Vitro Diagnostics
CD38 Diagnostic Tool
PCR-based genetic test to predict patient response to CD38 monoclonal antibodies
ACCURATE
SIMPLE & POWERFUL
Overview of CD38 Diagnostic
In vitro screening tool to be used prior to initiation of mAb therapy.
Quick and easy DNA test that delivers accurate, meaningful insights.
Enables more cost-effective, data-driven medical decisions
Potential to expand to a wide array of mAb therapies.