SEA-CD40

Overview

SEA-CD40 is a fully humanized non-fucosylated IgG1 monoclonal antibody (mAb) specific for CD40. SEA-CD40 exhibits superior antagonistic activity against CD40L in vitro and exhibits anti-tumor efficacy in xenograft animal models. Currently, the safety and tolerability of SEA-CD40 have been evaluated in clinical phase I dose escalation studies in patients with multiple solid tumor such as non-small-cell lung carcinoma, pancreatic adenocarcinoma, and head and neck neoplasms.

ADCC Enhancement Technology for SEA-CD40

SEA-CD40 is a novel glycosylation engineered humanized anti-CD40 monoclonal antibody developed to meet the needs of new therapies with atopic dermatitis. The glycosylation process used to develop this agent is achieved by reducing the fucosylation in the Fc region of the mAb molecule, resulting in increased binding affinity of the agent for the FcγRIII receptor on immune effector cells.

Glycoengineering by defucosylation of immunoglobulin G oligosaccharides in the Fc region of SEA-CD40. Fig.1 Glycoengineering by defucosylation of immunoglobulin G oligosaccharides in the Fc region of SEA-CD40.

Mechanism of Action of SEA-CD40

SEA-CD40 is an Fc glycosylated antibody derived from dacetuzumab and shows a higher affinity for FcγRIIIa binding. The effect of SEA-CD40 is enhanced by polished ADCC activity, activation of immune responses, and induction of antigen-specific T cells. The following figure demonstrated the mechanism of action of SEA-CD40, that is, by binding antigen-presenting cells to CD40 to activate antigen-presenting cells, further activating T cells to kill tumors and enhancing anti-tumor immune responses.

Mechanisms of action of SEA-CD40.Fig.2 Mechanisms of action of SEA-CD40.

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT02376699 Recruiting Cancer
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Hematologic Malignancies
Hodgkin Disease
Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Melanoma
Neoplasms
Neoplasm Metastasis
Neoplasms, Head and Neck
Neoplasms, Squamous Cell
Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer Metastatic
Non-small Cell Carcinoma
Squamous Cell Cancer
Squamous Cell Carcinoma
Squamous Cell Carcinoma of the Head and Neck
Squamous Cell Neoplasm
Lymphoma, Non-Hodgkin
Pancreatic Adenocarcinoma
Seattle Genetics, Inc. Phase I October 1, 2019

For more detailed information, please do not hesitate to contact us.

Reference

  1. K.A. Papp.; et al. Phase I randomized study of SEA-CD40, an anti‐CD40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol. 2017, Aug; 31(8): 1324–1332.

RESOURCES

Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details. 

All products and services are for Research Use Only. Do Not use in humans.

CASE STUDY

ADCC Assay WT vs AfucoTM Mabs  Visit

Resource

Antibody Fc Engineering: Towards Better Therapeutics  Visit

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