Three is a charm for an antibody to fight cancer

• Published in: Nature (London) Vol. 575; no. 7783; pp. 1B - 2B
• Main Authors: Garfall, Alfred L, June, Carl H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 21.11.2019
• Subjects: Antibodies; Antigens; Apoptosis; Binding sites; Cancer; CD28 antigen; CD3 antigen; CD38 antigen; Cell activation; Cell growth; Cytokines; Domains; Immune system; Immunoglobulins; Immunotherapy; Leukemia; Leukocytes; Lymphocytes; Lymphocytes T; Monkeys; Multiple myeloma; Myeloid cells; Plasma cells; Proteins; Tumor cell lines
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/d41586-019-03495-3

Wu and colleagues devised a clever strategy to simultaneously boost T-cell activation and enhance the targeting of cancer cells in relation to multiple myeloma, which is a cancer of plasma cells in the blood. The addition of a co-stimulatory signal such as CD28 is notable because this signal has also been incorporated into another type of immunotherapy called chimaeric-antigen receptor T cell (CAR-T) therapy5, in which a receptor is engineered to both recognize a cancer-cell antigen and include T-cell activation domains such as CD3 and CD28. The presence of the CD28-targeting domain on the antibody boosted the ability of T cells to kill different myeloma cell lines in vitro and in the humanized mouse model, even at the lowest antibody dose tested. [...]in terms of possible negative effects of the antibody on healthy non-cancerous cells, it is reassuring that only transient decreases in the number of normal white blood cells that express CD38, such as lymphocytes and myeloid cells, were observed in monkeys treated with the antibody.