Contact

Science

Antibodies against the sugars on cancer cells

Every cell is coated in sugars. When a cell turns malignant, that coat changes in ways specific enough to aim a therapy at.

01What TACAs are

What changes on a cancer cell

Glycans are chains of sugar molecules that sit on proteins and lipids on the cell surface. They shape how cells communicate with each other and with the immune system.

During malignant transformation, the machinery that builds these chains goes wrong. Cancer cells display short, truncated or unusual glycans: tumor-associated carbohydrate antigens, or TACAs.

Many TACAs are expressed during embryonic development but not under physiological conditions in differentiated tissue. On tumors they appear at very high density, which lets more of a therapeutic agent reach the cancer cell.

Healthy cell compared with tumor cell On healthy cells, glycans are long and branched. On tumor cells they are truncated into short structures, the tumor-associated carbohydrate antigens. An antibody binds these tumor-specific structures. HEALTHY TISSUE TUMOR CELL Full-length, branched glycans Truncated glycans: TACAs ADC with payload
Tumor-associated carbohydrate antigen Drug payload Schematic, not to scale.

02Why they matter

Why TACAs make good drug targets

Tumor selectivity
Found on cancer cells and largely absent from differentiated healthy tissue, which should allow higher doses with fewer side effects.
Pan-tumor presence
Highly expressed across many solid tumors, including pancreatic, gastric, colorectal, lung, ovarian and breast cancer.
Persistence
TACAs stay on tumor cells after standard therapies fail and in tumors without actionable genomic alterations.
Hard to escape
They support adhesion, immune evasion and metastasis. A tumor that masks or down-regulates them gives up functions it relies on.

03The problem

Why antibodies against them were hard to make

  1. 01

    Weak binding

    Antibodies usually bind carbohydrates with low affinity. For a therapy, that is not enough.

  2. 02

    Low immunogenicity

    The immune system barely reacts to these sugars, so classic immunization rarely yields good antibodies.

  3. 03

    No pure antigen

    Glycans isolated from cells are heterogeneous mixtures. Without pure, defined structures there is nothing precise to select against.

04Our platform

How the platform works

Tacalyx grew out of the work of Prof. Peter H. Seeberger and Dr. Oren Moscovitz at the Max Planck Institute of Colloids and Interfaces. The platform begins with the antigen: synthetic glycans, not material isolated from cells.

  1. STEP 01

    Synthesize

    Synthetic, ultra-pure and defined TACA structures in sufficient amounts, from Max Planck glycan chemistry.

  2. STEP 02

    Discover

    Screening for high-affinity antibodies that bind the tumor glycan and not its relatives on healthy cells.

  3. STEP 03

    Characterize

    Affinity, cell binding, internalization and expression in tumor and normal tissue decide which antibodies go forward.

  4. STEP 04

    Engineer

    The internalization rate points to the modality: an ADC for targets taken up quickly, a T-cell engager for those that stay on the surface.

05Modalities

Choosing the modality for each target

The platform delivers the antibody; the biology of the target decides the format. Tacalyx has taken one antibody into an ADC and another into a T-cell engager, and stays open to partners with their own payloads and formats.

Antibody-drug conjugates

The antibody carries a cytotoxic payload into the tumor cell, so the target has to internalize quickly. TCX-201, the first clinical candidate, is an ADC tested with MMAE, exatecan and deruxtecan payloads.

T-cell engagers

One arm binds the tumor glycan, another binds CD3 on T cells. This suits targets that stay on the cell surface, such as the sphingolipid-linked TACA of TCX-101.

Multi-specifics

Adding a tumor-associated protein antigen to the TACA arm makes binding depend on both targets. TCX-101 uses this in a trispecific T-cell engager.

06Data

Posters and talks

Each presentation has a short summary on this site and, where Tacalyx has released it, the poster as PDF.

07Roots and collaborations

Where the science comes from

Potsdam

Max Planck Institute of Colloids and Interfaces

The discoveries of Prof. Peter H. Seeberger and Dr. Oren Moscovitz in tumor glycoscience and glycan-targeting antibodies gave rise to the platform. Tacalyx spun out in 2019.

Munich

Max-Planck-Innovation

Technology transfer of the Max Planck Society. Licensor of the underlying technology and represented on the board.

Leiden

Leiden University Medical Center

Collaboration with Prof. Manfred Wuhrer's team on tumor-specific O-glycans in colorectal cancer, funded by a €500k Health~Holland grant.

See the pipeline Partnering