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
5071 - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma
Presenter: Soohyeon Kwon
Session: Poster Display session 3
Resources:
Abstract
5306 - Real-world data of clinicopathologic characteristics of young oropharyngeal cancer patients.
Presenter: Maria Nieva
Session: Poster Display session 3
Resources:
Abstract
3407 - The clinical significance and biological mechanisms of miR-499a in high-tobacco exposed head and neck squamous cell carcinoma
Presenter: Shiqi Gong
Session: Poster Display session 3
Resources:
Abstract
3310 - Liquid biopsy for mutational profiling of locoregional recurrent and/or metastatic squamous cell carcinoma of the head and neck
Presenter: Rachel Galot
Session: Poster Display session 3
Resources:
Abstract
2362 - Blood-based testing of mutations in patients with Head and neck squamous cell carcinoma (HNSCC) using highly sensitive SafeSEQ technology
Presenter: Florentia Fostira
Session: Poster Display session 3
Resources:
Abstract
4533 - The head and neck Lung Immune Prognostic Index (HN-LIPI): a prognostic Score for Immune Checkpoint Inhibitors (ICI) in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) patients.
Presenter: Ruth Gabriela Herrera Gomez
Session: Poster Display session 3
Resources:
Abstract
5262 - Immune-related adverse events (irAEs) and outcome in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) patients (pts) treated by immune-checkpoints inhibitors (ICI)
Presenter: Neus Baste Rotllan
Session: Poster Display session 3
Resources:
Abstract
3725 - Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy
Presenter: Jack Bui
Session: Poster Display session 3
Resources:
Abstract
2533 - A nomogram based prognostic score to predict overall survival (OS) in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients (pts) treated with immune checkpoint inhibitors (ICI).
Presenter: Luay Mousa
Session: Poster Display session 3
Resources:
Abstract
2929 - Changes of the Commensal Microbiome during Treatment are Associated with Clinical Response in the Nasopharyngeal Carcinoma Patients
Presenter: Tingting Huang
Session: Poster Display session 3
Resources:
Abstract