Antibody Against NY-BR1 with No Cross reactivity to NY-BR1.1 for Immunotherapy in Breast Cancer

Background

Immunotherapy in the field of cancer therapy aims to trigger an immune response that is targeting tumor cells. Monoclonal antibodies against tumor-specific antigens have become part of many cancer treatments. Besides, several different formats of immunoreactive molecules have been engineered. E.g. chimeric antigen receptor (CAR) molecules that have an antibody-derived antigen recognition domain and a T-cell activation domain are designed to give T-cells the ability to target a specific antigen. Patient derived CAR T-cells are produced ex vivo as cellular anti-cancer immunotherapies and are reinfused into the patient as a new option of treatment.

NY-BR1 is identified as a potential target for antibody-based therapies of breast cancer and is considered as well-suited for specific CAR T-cells.

Technology Overview

NY-BR1 is a promising target for antibody-based therapies of breast cancers. NY-BR1.1 and its Isoform 2 alters only in a single amino acid to NY-BR1 and is also expressed in healthy brain tissue. Cross-reactivity to NY-BR1-1 of antibodies targeting NY-BR1 therefore lead to the exclusion in the treatment of breast cancer of those antibodies in the CAR-format.

This invention is based on NY-BR1 targeting antibody which could also be used as bispecific antibody or for CAR T-cell therapy with no cross-reactivity to NY-BR1.1. The antibody 10D11 was generated by DNA vaccination of mice and via standardized hybridoma technology stable antibody producing cell lines were made (10D11 antibody (murin), 10D11 scFv-murinFc fusionprotein, 10D11 scFV- humanFc fusionsprotein and 10D11-CAR). Those constructs with dose-dependent sensitivity against NY-BR1 do not bind NY-BR1.1. Therefore, this invention provides improved immunoreactive molecules targeting NY-BR1 for the use in immunotherapy in cancer therapy.

Stage of Development

Pre‑clinical PoC

Further Detail

• Seil et al. “The differentiation antigen NY-BR-1 is a potential target for antibody-based therapies in breast cancer” Int J Cancer 2007 Jun 15; 120(12):2635-42).
• Jäger et al. “Novel chimeric antigen receptors for the effective and safe treatment of NY-BR-1 positive breast cancer.” Clin Transl Med. 2024 Jul;14(7):e1776. doi: 10.1002/ctm2.1776.

Benefits

• Antibody-based therapy targeting NY-BR1 for treatments of breast cancer
  • No cross-reactivity against NY-BR1.1 (also expressed in healthy brain tissue)

Applications

• Immunoreactive molecules for use in the treatment of breast cancer
• 10D11-CAR for CAR T-cell therapy
• Companion diagnostics of NY-BR1 (immunohistochemical staining, membrane-mediated protein blotting methods, flow cytometry based)

Opportunity

Collaboration, Licensing