Genentech Oncology
Tumors can employ mechanisms that alter the immune response in their microenvironment.1 One approach to countering these immuno-evasive mechanisms is to redirect and expand populations of T cells.2,3 T cells can be physically recruited and linked to tumor surface antigens to elicit an antitumor immune response in patients with cancer.4 Bispecific antibodies are designed to simultaneously bind to T cells and tumor cell antigens, leading to T-cell activation, proliferation, and tumor cell death.4
Bispecific antibodies targeting a variety of tumor types have become an important component of Genentech's investigational cancer immunotherapy research. In contrast to early-generation therapeutic antibodies, bispecific antibodies combine the binding specificity of two antibodies in one molecule.5 They are engineered to have two or more distinct Fab regions (antigen-binding sites) with a common Fc region. This structure allows simultaneous binding to CD3 on T cells and target antigens on tumor cells, which brings the T cells into close proximity with the target tumor cells, leading to T-cell–mediated killing of the tumor cells.3,4
CEA=carcinoembryonic antigen; Fab=fragment of antigen binding; Fc=fragment, crystallizable.
We are exploring the potential of innovative bispecific antibody structures that activate T cells to induce an antitumor immune response across multiple tumor types.5,6
Simultaneous binding of a T-cell bispecific antibody to CD3 on T cells and a tumor cell surface antigen, such as CEA or CD20, may result in the formation of an immune synapse, a junction formation between the T cell and tumor cell, and subsequent downstream signaling that may lead to T-cell–mediated tumor killing through:3,4
We are exploring the potential of combining T-cell bispecific antibodies with other anticancer therapies, including PD-L1 inhibition and antibody drug conjugates in the pursuit of enhancing T-cell–mediated cancer immunity.
Watch a time-lapse microscope video of the T-cell bispecific antibody in activating cytotoxic T lymphocytes designed to kill tumor cells. As demonstrated in preclinical models, upon dispersion of T-cell bispecific antibodies, the cytotoxic T cells (seen in red) immediately recognize and begin to destroy the target cancer cells (seen in blue). Green flashes in the tumor cells indicate imminent T-cell–induced cell death.8
Watch a time-lapse microscope video of the T-cell bispecific antibody activating cytotoxic T lymphocytes designed to kill tumor cells.
This compound and its use continue to be investigated in ongoing studies; efficacy and safety have not been established.
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17:385-392. PMID: 23623807
Frankel SR, Baeuerle PA. Targeting T cells to tumor cells using bispecific antibodies. Curr Opin Chem Biol. 2013;17:385-392. PMID: 23623807
Bacac M, Klein C, Umana P. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
Bacac M, Klein C, Umana P. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
Bacac M, Fauti T, Sam J, et al. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
Bacac M, Fauti T, Sam J, et al. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20:838-847. PMID: 25728220
Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20:838-847. PMID: 25728220
Sun LL, Ellerman D, Mathieu M, et al. Sci Transl Med. 2015;7:287ra70. PMID: 25972002
Sun LL, Ellerman D, Mathieu M, et al. Sci Transl Med. 2015;7:287ra70. PMID: 25972002
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
Junttila TT, Li J, Johnston J, et al. Antitumor efficacy of a bispecific antibody that targets HER2 and activates T cells. Clin Cancer Res. 2014;74:5561-5571. PMID: 25228655
Junttila TT, Li J, Johnston J, et al. Antitumor efficacy of a bispecific antibody that targets HER2 and activates T cells. Clin Cancer Res. 2014;74:5561-5571. PMID: 25228655
Learn more about the importance of oncologic biomarkers and what they can tell you.
Learn more about how cancer avoids immune response.
The compounds and their uses mentioned on this website are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. Do you wish to proceed?
The link you have selected will take you away from this site to one that is not owned or controlled by Genentech, Inc. Genentech, Inc. makes no representation as to the accuracy of the information contained on sites we do not own or control. Genentech does not recommend and does not endorse the content on any third-party websites. Your use of third-party websites is at your own risk and subject to the terms and conditions of use for such sites.