Abstract 2416
Background
CEACAM1 is a member of the CEA family expressed in cell membranes of T cells and NK cells as well as tumor cells. CEACAM1 overexpressed in tumor cells interacts with CEACAM1 expressed in tumor infiltrating lymphocytes (TIL) and suppresses TIL activity by sending an inhibitory signal to immune cells, which is an immune escape mechanism in cancer. Therefore, we developed MG1124, a monoclonal antibody that specifically binds to CEACAM1 but not to other CEA family members, thereby blocking tumor growth by triggering immune response.
Methods
CEACAM1 specific binding of MG1124 was tested in CEACAM1 or other CEA family over-expressing cells. MG1124 was examined by in vitro tumor cell lysis assays using NK92, a human NK cell line. The anti-tumor efficacy of MG1124 alone or in combination with a PD-1 inhibitor was studied in a humanized mouse model engrafted with non-small cell lung cancer (NSCLC) patient-derived tumor xenografts (NSCLC hu-PDX models).
Results
An anti-CEACAM1 antibody, MG1124 binds to CEACAM1 overexpressing Jurkat cells but not to other CEA family members and blocks ligands interaction in a dose-dependent manner. MG1124 increased NK92-mediated tumor cell lysis against cancer cells with strong CEACAM1 expression, but not to those with no or weak CEACAM1 expression. In a single mouse trial, MG1124 (tumor growth inhibition (TGI) 55%) was efficacious in the high CEACAM1 expressing NSCLC hu-PDX model as monotherapy. In addition, the combination therapy (TGI 42%) with a PD-1 inhibitor displayed enhanced antitumor activity than the anti-CEACAM1 monotherapy (TGI 17%) in a CEACAM1-low expression model as well as in a CEACAM1-high expression model (combination therapy TGI 63% vs monotherapy TGI 46%). Moreover, tumor tissues (n = 150) of NSCLC patients showed extensive expression of CEACAM1, suggesting a potential therapeutic use of MG1124 in NSCLC patients.
Conclusions
In this study, the anti-CEACAM1 antibody MG1124 showed antitumor efficacy in human CEACAM1-expressing cancer cell lines and NSCLC hu-PDX xenograft models, and demonstrated potential as a targeted therapy for NSCLC, both as a single agent and in combination with a PD-1 inhibitor.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3073 - 1 patient 3 different advance Ca nurse’s roles: symptom management&continuum care through a joint approach in a clinical case
Presenter: Catarina Almeida
Session: Poster Display session 3
Resources:
Abstract
4527 - Identification of malnutrition risk factors in patients with cancer in the first nursing visit
Presenter: Amaia Valverde
Session: Poster Display session 3
Resources:
Abstract
2904 - Engaging Cancer Survivors, Healthcare Providers and Advocates in The Development of a Colorectal Cancer Survivorship Information Resource: A Participatory Action Research Study
Presenter: Amanda Drury
Session: Poster Display session 3
Resources:
Abstract
3435 - Medical nurses’ experiences of the care-needs of adult patients with a primary brain tumour
Presenter: Jamila Mohammed
Session: Poster Display session 3
Resources:
Abstract
857 - Feasibility and acceptability of a mHealth intervention to increase colonoscopy uptake among Chinese first-degree relatives: a pilot cluster randomized controlled trial
Presenter: Yang Bai
Session: Poster Display session 3
Resources:
Abstract
1087 - Cancer patient participation and compliance in microbiome sample collection: an oncology research nurse’s experience
Presenter: Julie Malo
Session: Poster Display session 3
Resources:
Abstract
2783 - Implementing Digital Individual Care plans for Patients with Head and Neck cancer- Challenges and opportunities
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract
1152 - The Effect of the Short-term and Long-term Compassion Fatigue Resiliency Program on the Quality of Life, Perceived Stress and Psychological Resilience of Oncology-Hematology Nurses
Presenter: Tugba Pehlivan
Session: Poster Display session 3
Resources:
Abstract
1172 - Competing risk analyses of overall survival and cancer-specific survival in patients with orbital rhabdomyosarcoma after surgery: a large cohort study
Presenter: Yu Zhang
Session: Poster Display session 3
Resources:
Abstract
5949 - Communication of genetic information to family members in hereditary cancers and healthcare providers’ role
Presenter: Carla Pedrazzani
Session: Poster Display session 3
Resources:
Abstract