Designed protein logic to target cells with precise combinations of surface antigens

Author:

Lajoie Marc J.12ORCID,Boyken Scott E.12ORCID,Salter Alexander I.34ORCID,Bruffey Jilliane125ORCID,Rajan Anusha34ORCID,Langan Robert A.12ORCID,Olshefsky Audrey16ORCID,Muhunthan Vishaka34ORCID,Bick Matthew J.12ORCID,Gewe Mesfin4ORCID,Quijano-Rubio Alfredo126ORCID,Johnson JayLee1,Lenz Garreck1ORCID,Nguyen Alisha1,Pun Suzie67ORCID,Correnti Colin E.4ORCID,Riddell Stanley R.348ORCID,Baker David129ORCID

Affiliation:

1. Institute for Protein Design, University of Washington, Seattle, WA, USA.

2. Department of Biochemistry, University of Washington, Seattle, WA, USA.

3. Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

4. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

5. Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, USA.

6. Department of Bioengineering, University of Washington, Seattle, WA, USA.

7. Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA, USA.

8. Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

9. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.

Abstract

Logic at the cell surface A major challenge in medical interventions is to target only diseased cells. Although there are biomarkers characteristic of certain cancers, for example, it is unlikely that a single marker can specify a particular cell type. Lajoie et al. addressed this problem by designing protein switches called Co-LOCKR that bind to antigens on the cell surface and activate through a conformational change only when there is a precise combination of antigens. They designed switches that can perform AND, OR, and NOT logic. On the path toward applying this technology, they used Co-LOCKR to direct chimeric antigen receptor T cells to tumor cells expressing specific antigens. Science , this issue p. 1637

Funder

National Science Foundation

National Institutes of Health

Howard Hughes Medical Institute

National Cancer Institute

Burroughs Wellcome Fund

Defense Threat Reduction Agency

Washington Research Foundation

Open Philanthropy Project

Nordstrom Barrier IPD Directors Fund

Audacious Project organized by TED

Fred Hutchinson Cancer Research Center

Hearst Foundations

Cancer Research Institute

National Institute of General Medical Sciences

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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