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Forging New Breakthroughs in Lifesaving Immunotherapies

Our Proprietary Cell Therapy Technology Platforms

The induced Pluripotent Stem Cell (iPSC) is one of the most recent and advanced approaches to cellular immunotherapies. With intelligent engineering, we have developed the iPSC-derived natural killer (iNK) cells and macrophages (iMACs) that we expect to become cellular immunotherapies that will lead the fight in oncology.

Optimizing the cells with precise and rational genetic reprogramming, cellular immunotherapies will be designed to effectively and efficiently target and kill tumors and repair tissue homeostasis. This approach, based on the fundamental advantage of iPSC cell engineering and expansion, is forging the way for a more streamlined, affordable, and scalable manufacturing process that can deliver treatments to patients in the most cost-effective, time-saving manner.

Harnessing the Most Powerful Cells of the Immune System

iNK cells have a natural ability to identify and kill tumor cells while producing cytokines that recruit and activate the immune response. They have fail-safe mechanisms that prevent the killing of healthy cells, making NK cells a promising and important avenue for future cell therapy development.

Shoreline has developed iPSC-derived iNK cells that are genetically engineered for improved performance in patients compared with donor-derived NK cells. This includes greater activity, metabolic fitness, persistence, and resistance to exhaustion. We expect this advance in cell therapy to have a significant impact on patient outcomes.

Shoreline is also developing iPSC-derived iMACs for oncology and non-oncology indications. These cells are designed to clear malignant or damaged cells and regulate immune recruitment to restore tissue homeostasis.

Components of Our iNK Cell Platform

Our iPSC-based approach creates a modular system whereby each program can serve as a foundation for further gene editing, which we believe enables the rapid development of a robust pipeline. In this fashion, our CISH KO iNK master cell bank, or MCB, will serve as a foundation for multiplexed editing to generate additional NK cellular immunotherapy products. We believe these edits have the potential to convey additional unique benefits to further optimize the therapeutic profile of our NK-based cellular immunotherapies in both hematologic and solid tumors.

Engineered iPSC - NK Cells

NK Optimized CAR

Optimized for ADCC

Universal Engagers

Engineered iPSC NK Cells

Our advanced proprietary process of genetic modification to iPSC-derived NK cells allows for precise genetic reprogramming and has proven in research studies to enhance the NK cell’s ability to sustain a longer life span with greater fighting power.

The first of these genetic modifications begin with the cell’s engine, by knocking out specific genes (CISH) that regulate NK cell functionality. We are exploring additional gene edits that will further enhance NK cell performance.

NK Cell Engine 1

  • Persistence
  • Metabolic Activity
  • Polyfunctionality
  • Reduced Cell Exhaustion

NK Cell Engine 2

  • Stabilized CD16
  • Cytotoxicity
  • Tissue Homing
 

Engineered iPSC NK Cells with Optimized for CARs

To further enhance the iPSC-derived NK cell’s ability to target and destroy toxic cells, we have developed a series of proprietary tumor targeting Chimeric Antigen Receptors (CARs) that work synergistically with the new genetic signature of the iPSC-derived CISH-KO NK cells.

These tumor targeting CARs engage specific tumor associated antigens directly, via the antigen-binding fragment (scFv), and activate the NK cells through optimized intracellular signaling modules.

NK Cell Specific CARs

 
 

Engineered iPSC NK Cells Optimized for ADCC

The iPSC-derived NK cells can also be targeted to tumors with monoclonal antibodies to trigger Antigen-Dependent Cellular Cytotoxicity (ADCC). We are developing iPSC-derived NK cells that are optimized for enhanced ADCC activity to lead to tumor clearance alone or work in combination with CAR signaling.

Universal Receptor + Tumor Targeting Switches

Multi-antigen Tumor Targeting

 

Universal Engagers

Our unviersal technology allows us to direct our iPSC-derived NK cells to different tumor antigens inside a patient. With this technology we are no longer chasing tumor evolution in the traditional methods, but are developing cellular immunotherapies that may treat multiple antigens at once. We expect that, if developed, cellular immunotherapies based on universal, scalable application will allow for a personalized off-the-shelf treatment protocol for each patient.

Engineered iPSC NK Cells

Our advanced proprietary process of genetic modification to iPSC-derived NK cells allows for precise genetic reprogramming and has proven in research studies to enhance the NK cell’s ability to sustain a longer life span with greater fighting power.

The first of these genetic modifications begin with the cell’s engine, by knocking out (KO) specific genes (CISH), which enhance the cells functionality.

iPSC NK Cells Optimized for CARS

To further enhance the iPSC-derived NK cell’s ability to target and destroy toxic cells, we’ve developed a series of proprietary tumor targeting and homing Chimeric Antigen Receptors (CARs) that work synergistically with the new genetic signature of the iPSC-derived CISH-KO NK cells.

These tumors targeting CARs attach to and engage the expressed antigens of the tumor directly via the antigen-binding fragment (scFv). The intracellular protein segments act as signaling devices to communicate with the cell to undergo a cascade of effects, releasing cytokines which begin the process of antigen destruction.

Optimized for ADCC

Another tumor targeting device is Antigen-Dependent Cellular Cytotoxicity (ADCC) attaches to the expressed antigens of the tumor indirectly through the assistance of monoclonal antibodies that have been injected into patients. Once they traffic to and attach to the tumor, the intracellular signaling of these CARs informs the NK cell to release cytokines to kill the tumor.

Each CAR construct is rationally designed to enhance binding affinity to the tumor antigens or antibodies and optimize cell activation signaling to kill the tumor.

Universal Engagers

The antigen-binding fragments of the Universal Engagers are able to interact universally with any number of antibodies or switches injected into the body. As the tumor evolves and expresses new antigens, these Universal Engagers are able to attach to any antibody switch and signal intracellular activity to destroy the tumor.

First-In-Class iPSC-Derived Macrophage Cells

Macrophages are sentinel innate immune cells that can kill tumor cells while orchestrating the anti-tumor immune response. The role of macrophages in tumor biology is not one sided, however, and tumor associated macrophages are a major component of the tumor microenvironment that prevents immune clearance.

Shoreline’s iPSC derived “M1” macrophages are genetically enhanced for optimal anti-tumor functionality. These cells traffic to tumors where they modulate the tumor microenvironment to be pro-inflammatory and marshal additional immune effector cells to drive tumor clearance.

Macrophage biology can also be utilized to treat non-oncology indications. Our iPSC derived “M2” cells can be used in regenerative therapy, fibrosis and inflammatory diseases.

Anti-Tumor Activity of iPSC Derived Macrophages

Selection & Differentiation

Genetically engineered iPSCs are SELECTED & DIFFERENTIATED into tumor targeting macrophages and frozen for cryopreserved  

Modulation & Marshalling

iPSC-derived Macrophages traffic to the tumor where they MODULATE the immune-suppressive micro-environment & MARSHAL a broader immune response

Phagocytosis, Presentation & Clearance

iPSC-derived Macrophages PHAGOCYTOSE tumor cells and PRESENT tumor antigens to the evolving immune response – an essential step towards permeant TUMOR CLEARANCE  

We are partnered with the Advanced Cell Therapy Laboratory (ACTL) of UC San Diego

ACTL is a well-recognized manufacturing facility.
Their state-of-the-art GMP and GLP systems and facilities allow for accelerated product development from research and development to compliant and clinically relevant manufacturing of cell therapy products.
ACTL is equipped with manufacturing suites to enable product segregation and multi-lot production and has nitrogen storage freezers suitable for long-term storage of cellular products in vapor-phase.
This partnership allows us to bring in-house GMP grade iPSCs to bank and rapidly initiate preclinical development and IND-enabling studies.
We also have an extensive network of CMC/Manufacturing professionals with over 20 years of experience that we leverage for manufacturing and development plans and strategies for cell therapies.

Intelligently Engineered Cells Designed to Give Rise to Accessible, Lifesaving Therapies