Bispecific Antibody Cellular Therapy Displays Anti-tumor Activity Against Lympho

Posted by beauty33 on July 11th, 2021

Researchers at the University of Texas MD Anderson Cancer Center recently conducted a preclinical study on combining cytokine-activated natural killer (NK) cells derived from donated umbilical cord blood with an investigational bispecific antibody (known as AFM13) targeting CD16a and CD30. The result of bispecific antibody cellular therapy displayed potent anti-tumor activity against CD30+ lymphoma cells.

NK cells are part of the innate immune system, known for killing cells infected by viruses, detecting early signs of cancer, and playing an important role in pregnancy. However, it is worth noting that tumors are very likely to develop mechanisms to evade NK cells that have limited persistence by nature.

The finding was published in Clinical Cancer Research, leading to the launch of phase I clinical trial to explore experimental cell-based immunotherapy in patients with CD30+ lymphoma.

Antibody therapy proves to be highly powerful for cancer treatment based on two important cell killing mechanisms, antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC). Therefore, it's of vital importance to perform CDC assay and ADCC assay to see if therapeutic bsAb candidates can efficiently induce the cell killing mechanism.

In this study of bispecific antibody cellular therapy for lymphoma cells, the team also used mass cytometry and cytotoxicity assays to assess single-cell NK cell responses stimulated by the AFM13 bispecific antibody that binds to CD30 on leukemia/lymphoma targets and CD16A on various types of NK cells.

Bispecific antibody fragments with or without certain antibody constant domains are the combination of antigen-binding units. With high affinity and multiple valences to different targets, they are widely used in both academic and preclinical applications. For instance, AFM13 used in the clinical trial is a tetravalent BsAb in tandem diabody (TandAb) format without Fc domain, and it is proprietorially designed to bind to CD16a on NK cells and CD30 on lymphoma cells.

Experiments in animal models display an improved tumor control and survival, making this investigational bispecific antibody cellular therapy an anticipatory benefit to patients with advanced lymphoma in the ongoing clinical trial.

In spite of the promising result, researchers still worried about the possible side effects. Fortunately, further research proved that cord blood-derived NK cells (cbNKs) combined with AFM13 displayed consistent and improved activity against lymphoma, with minimal side effects observed, relative to other NK cell sources.

Actually, bispecific antibodies have displayed several potent clinical results. It's estimated 50 clinical trials using bsAbs for various malignancies are now underway, meanwhile, numerous biotechnology companies like Creative Biolabs and academic labs purportedly have engaged in related product development and drug testing. In terms of these applications in immunotherapy, comprehensive bsAb analysis of quality, stability, property, etc. is still one of the most important parts of the procedures.

l Biochemistry Characterization

Biochemistry characteristic analysis will measure the purity, molecular weight/mass, molecular structure, which is an essential part to successfully develop bsAb based biopharmaceuticals in both basic and clinical fields.

l Stability Analysis

Stability analysis covers aggregation measurement, thermal stability measurement, and in vitro serum stability measurement. Protein aggregation affects drug potency and desired immune effects.

l Functional Analysis

The functional analysis includes target binding affinity measurement, ADCC assay, CDC assay, and antibody-dependent cellular phagocytosis (ADCP) assay.

Many other analyses and research are also necessary, such as absorption analysis, distribution analysis, metabolism and elimination analysis, and preclinical research on cell cultures, animals, healthy human subjects, etc.

To sum up, it's definitely a piece of inspiring news for both researchers and patients with advanced lymphoma that NK cells combined with bispecific antibodies display potent anti-tumor activity. To satisfy the treatment needs of both hematologic cancers and solid tumors, more dedication should be put in cytotoxicity assays, drug quality analysis, and, further clinical testing.