Fully Human Antibody Binders to CD66e (CEACAM5)

This invention is a set of antibody-based binders that recognize CD66e (CEACAM5), a cell-surface protein found on many solid tumors. The same binding domains can be built into antibodies, CAR cells, T cell/NK cell engagers and antibody-drug conjugates, giving several routes to targeted cancer treatment.

Description

The technology centers on two defined antibody binding domains. Each pairs a set of three heavy-chain and three light-chain complementarity-determining regions (CDRs), the parts of an antibody that recognize its target. Both bind the CD66e protein. CD66e is a cell-adhesion protein highly expressed in several cancers, including neuroendocrine prostate cancer.

The binding domains work as a modular platform. They can be used as a full antibody or antibody fragment. They can also serve as the targeting element of a chimeric antigen receptor (CAR), a receptor engineered into T cells, stem cells or NK cells so they recognize tumor cells. In a cell engager, one arm binds CD66e and the other recruits immune cells, either T cells through CD3 or NK cells through CD16a, NKG2A, NKG2D, NKp30, NKp44 or NKp46. In an antibody-drug conjugate (ADC), the binder is covalently linked to a drug so it can be delivered to CD66e-bearing cells. The binders can be used to treat a mammal with cancer or to bind CD66e polypeptide in vitro or in vivo.

Applications

- CD66e-targeted therapeutic antibodies for solid tumors
- CAR-T, CAR-NK and CAR-stem cell therapies directed to CD66e-expressing cancers
- T cell and NK cell engagers (bispecific or multispecific) for immune-mediated tumor killing
- Antibody-drug conjugates for targeted payload delivery to CD66e-positive cells
- Research and development reagents for binding CD66e polypeptide

Advantages

- Defined binding domains (two CDR sets) that bind CD66e
- One binder usable across several formats: antibody, antibody fragment, CAR, cell engager and ADC
- Can engage either T cells or NK cells through the cell engager design
- Compatible with multiple CAR host cells (T cells, stem cells, NK cells) and scFv or IgG formats
- Supports targeted drug delivery as an ADC and treatment of cancer in a mammal

Invention Readiness

In vivo data

IP Status

https://patents.google.com/patent/US12703760B2

Related Publication(s)

Baek, D.-S., Kim, Y.-J., Vergara, S., Conard, A., Adams, C., Calero, G., Ishima, R., Mellors, J. W., & Dimitrov, D. S. (2022). A highly-specific fully-human antibody and CAR-T cells targeting CD66e/CEACAM5 are cytotoxic for CD66e-expressing cancer cells in vitro and in vivo. Cancer Letters, 525, 97–107. https://doi.org/10.1016/j.canlet.2021.10.041