Scientific Background

Cells sense and respond to their enviornment

Cells, including immune cells, are constantly interacting with their environment, a process called mechanosensation. Their surrounding is dynamic and subject to various mechanical forces, such as tissue stiffness, blood flow, shear stress, and cellular interactions. In a tumor, this environment is strongly changed so that immune cells often lose their function. We are working towards equipping cells with the capacity to overcome these limitations.

Unique mechano-stimuli for T cell activation

T cells, a type of immune cell, usually requires biochemical stimuli for their activation process, where they form an immune synapse. The formation and stability of this immune synapse depend on mechanical forces. Enhanced T cell activation in vitro can be achieved when combining biochemical with optimized mechanical stimuli. immUni solution exploits this mechanosensation properties resulting in superior T cell activation and quality.

Our Product

Ready-to-use cell culture dish (R&D)
  • Unique technology: Novel Mechanism of action
    • Mechanical stimulation

  • Advancing production: "All in one, all at once"
    Better production performance
    • Major reduction of production steps

    • Faster and cost saving

  • Our mission: Improved cell fitness and therapeutic efficacy
    • Promising against solid tumors

Applications

immUni solution for personalized cellular therapies

Advanced cell therapies

Cell advanced therapies are innovative medical approaches that utilize living cells to treat diseases and medical conditions. These therapies often involve genetically modifying or manipulating cells to enhance their therapeutic potential. They encompass various techniques, including gene therapy, cell therapy, and tissue engineering, each tailored to address specific medical needs. Cell advanced therapies hold significant promise in regenerative medicine, enabling the repair, replacement, or regeneration of damaged tissues and organs. Despite their potential, extensive research and rigorous clinical trials are essential to ensure their safety and efficacy before widespread adoption in medical practice.

CAR-T cell therapies (Chimeric Antigen Receptor T-cell therapy)

CAR-T cell therapies are the biggest advanced cell therapeutic sector. This therapy is an innovative and highly promising form of immunotherapy used to treat certain types of cancer. It involves genetically modifying a patient's own T cells (autologous) or universal "off-the shelf" T cell lines (allogeneic) to express a chimeric antigen receptor (CAR) on their surface. The CAR is designed to recognize and bind to specific proteins present on cancer cells, leading to their destruction. ​ CAR-T cell therapy has shown remarkable success in treating certain types of blood cancers, particularly relapsed or refractory acute lymphoblastic leukemia (ALL) and certain types of non-Hodgkin lymphoma. Some CAR-T cell therapies have also been approved for other indications and ongoing research is exploring their potential for treating various solid tumors.

CAR-T cell unmet needs

Complex manufacturing a critical bottleneck for therapeutic development

CAR-T cell therapy has transformed blood cancer treatment with promising clinical trial outcomes. However, access to this therapy has been limited due to lengthy and complex CAR-T cell production processes, resulting in a very costly therapy. To enhance patient welfare, establishment of innovative point-of-care solutions with a simplified and shortened manufacturing processes will be crucial to ensure higher cell quality and a shorter vein-to-vein time.

Collection
of T cells

Step 1

Activation

Step 2

Genetic modification

Step 3

CAR-T cell expansion

Infusion of
CAR-T cells

Production steps of CAR-T cell therapy

Collection of T cells: The patient's T cells (immune cells) are collected through a process called leukapheresis. Blood is drawn from the patient, and T cells are separated from the rest of the blood components using a specialized machine. Alternatively, new therapies using "of-the-shelf" allogenic cells (not from the patient) are currently under development.

Step 1. Activation: T cell activation for CAR-T production involves stimulating T cells with specific antigens or antibodies against the T cell receptor, commonly referred to as biochemical stimulation. This activation is step crucial in order for these cells to be further genetically modified and expanded.​

Step 2. Genetic modification: T cells are genetically modified to express the chimeric antigen receptor (CAR) on their surface. The CAR is typically composed of an extracellular domain that targets a specific protein or antigen present on cancer cells, a transmembrane domain, and an intracellular domain that activates the T cell upon binding to the target antigen.

Step 3. CAR-T cell expansion: The modified T cells are cultured and expanded in the lab, creating a large population of CAR-expressing T cells. This lengthy process (few weeks) compromises cell fitness the longer it takes. Thus novel methods are currently aiming to expand the CAR-T cells in-vivo (already in the patients body). Despite considerably shortening the production process in-vivo expansion still critically depends on the quality of cells obtained from earlier steps.

Infusion of CAR-T cells: Once the CAR-T cells have been expanded and the patient has undergone conditioning treatment, i.e. chemotherapy or other treatments to deplete some of the existing immune cells, the CAR-T cells are infused back into the patient through an intravenous (IV) infusion.

Solution

Novel nano-engineered platforms allowing to combine and enhance key steps of the CAR-T production

From T cell activation, gene transfer to expansion. immUni platform integrates a unique combination of biochemical and physical stimulation. The biophysical activation is achieved without the need for a T cell receptor agonist, resulting in a striking balance between robust T cell activation, proliferation , T cell effector function and most importantly a less differentiated phenotype required for CAR-T cell therapy. immUni technology is an easy-to-use platform that minimizes benchwork.

Cancer
Patient

+125%

Robust Activation

+90%

Optimized Gene
Delivery

+120%

Faster Expansion

Patient
Treatment

Disruptive Technology

Head-to-head comparison between immUni substrates and established activation methods for CAR-T production
  • Benchmark results of immUni solution solely coated with aCD28-antibody against DynabeadsTM (Thermo Fisher Scientific)

  • ​½ activation time: shorter activation time of immUni 24 h versus 72 h with further potential to combine activation and transfection steps​

  • >80% increased CD69 expression after activation on immUni substrates: T cells showed high percentages of CD69 expressing cells while maintaining lower MFI values​

  • 90% improved gene transfer efficiency: using lentiviral transduction more CD19 CAR-positive CAR-T were obtained with immUni solution after 6 days post

  • 120% higher Il-2 secretion: enhanced secretion on immUni substrates after 24 h​

  • 2X higher fold expansion: after 10 days and upon 24h activation only immUni substrates

  • ​120% more of the T cells maintain a less differentiated CCR7 positive phenotype: This outcome holds great promise for long-term tumor control.

Product Pipeline

immUni seeks continously contributing to support the developement of advanced cell therapies​

Besides contributing to advance research and development in the sector of advanced cell therapies in particular CAR-T cell, we aim to further develop our own medical device for new generations of clinical point-of-care treatment.​ The potential of immUni solution within cell advanced therapies is not exclusive to the CAR-T cell selector, allowing to diversify into additional areas, such Natural Killer cells and B cells. We further seek contributing to improve cell therapies beyond cancer treatment.

CAR-T

Final development of the first R&D Product

Initiated development

Customized Clinical Solution

B-cell

R&D Product initiated

NK-cell

R&D Product to be confirmed

Selected Publications

Zünd T, Lickert S, Strebel A, Murner M, Willms T, Simsek H, Du W, Wagner DL, Vogel V, Klotzsch E. (2023) Nanoporous Substrates to Advance CAR-T Cell Production for Advanced Cell Therapies.
28.11.2023 Learn More
Aramesh M, Stoycheva D, Sandu I, Ihle S, Zünd T, Shiu J, Forro C, Asghari M, Bernero M, Lickert S, Oxenius A, Vogel V, Klotzsch E. (2021), Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation. Proc. Natl. Acad. Science U.S.A., 118 (40) e2107535118
25.09.2023 Learn More
Simsek, H.; Klotzsch, E#. The Solid Tumor Microenvironment – Breaking The Barrier For T Cells .
25.09.2023 Learn More

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