Antibodies as drugs-a Keystone Symposia report

Jennifer Cable¹, Erica Ollmann Saphire^{2

3}, Adrian C Hayday^{4

5

6}, Timothy D Wiltshire⁷, Jarrod J Mousa^{8

9

10}, David P Humphreys¹¹, Esther C W Breij¹², Pierre Bruhns¹³, Matteo Broketa¹³, Genta Furuya¹⁴, Blake M Hauser¹⁵, Matthieu Mahévas¹⁶, Andrea Carfi^{17

18}, Tineke Cantaert¹⁹, Peter D Kwong²⁰, Prabhanshu Tripathi²⁰, Jonathan H Davis²¹, Neil Brewis²², Bruce A Keyt²³, Felix L Fennemann²⁴, Vincent Dussupt^{25

26}, Arvind Sivasubramanian²⁷, Philip M Kim^{28

29}, Reda Rawi²⁰, Eve Richardson³⁰, Daniel Leventhal³¹, Rachael M Wolters³², Cecile A W Geuijen³³, Matthew A Sleeman³⁴, Niccolo Pengo³⁵, Francesca Rose Donnellan³⁶

Affiliations

¹ PhD Science Writer, New York, New York, USA.
² Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.
³ Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁴ Peter Gorer Department of Immunobiology, King's College London, London, UK.
⁵ Cancer Research UK Cancer Immunotherapy Accelerator, London, UK.
⁶ Immunosurveillance Laboratory, The Francis Crick Institute, London, UK.
⁷ Mayo Clinic, Rochester, Minnesota, USA.
⁸ Department of Infectious Diseases and Center for Vaccines and Immunology, College of Veterinary Medicine, Athens, Georgia, USA.
⁹ Department of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia, USA.
¹⁰ Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ Protein Sciences, UCB Pharma, Berkshire, UK.
¹² Translational Research and Precision Medicine, Genmab BV, Utrecht, the Netherlands.
¹³ Institut Pasteur, Université de Paris, Unit of Antibodies in Therapy and Pathology, Paris, France.
¹⁴ Department of Preventive Medicine and Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
¹⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
¹⁶ Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
¹⁷ Moderna Inc., Cambridge, Massachusetts, USA.
¹⁸ Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
¹⁹ Immunology Unit, Institut Pasteur du Cambodge, The Pasteur Network, Phnom Penh, Cambodia.
²⁰ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Invenra, Inc, Madison, Wisconsin, USA.
²² F-star Therapeutics Ltd., Cambridge, UK.
²³ IGM Biosciences, Inc., Mountainview, California, USA.
²⁴ Lava Therapeutics, Utrecht, the Netherlands.
²⁵ Emerging Infectious Diseases Branch, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
²⁶ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
²⁷ Computational Biology, Adimab, Palo Alto, California, USA.
²⁸ Department of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.
²⁹ Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
³⁰ Department of Statistics, University of Oxford, Oxford, UK.
³¹ Generate Biomedicines, Somerville, Massachusetts, USA.
³² Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³³ Merus N.V., Utrecht, the Netherlands.
³⁴ Regeneron Pharmaceuticals, Tarrytown, New York, USA.
³⁵ Mabylon AG, Schlieren, Switzerland.
³⁶ University of Oxford, Oxford, UK.

PMID: 36382536
PMCID: PMC10103175
DOI: 10.1111/nyas.14915

Antibodies as drugs-a Keystone Symposia report

Jennifer Cable et al. Ann N Y Acad Sci. 2023 Jan.

. 2023 Jan;1519(1):153-166.

doi: 10.1111/nyas.14915. Epub 2022 Nov 16.

Authors

Affiliations

¹ PhD Science Writer, New York, New York, USA.
² Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.
³ Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁴ Peter Gorer Department of Immunobiology, King's College London, London, UK.
⁵ Cancer Research UK Cancer Immunotherapy Accelerator, London, UK.
⁶ Immunosurveillance Laboratory, The Francis Crick Institute, London, UK.
⁷ Mayo Clinic, Rochester, Minnesota, USA.
⁸ Department of Infectious Diseases and Center for Vaccines and Immunology, College of Veterinary Medicine, Athens, Georgia, USA.
⁹ Department of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia, USA.
¹⁰ Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ Protein Sciences, UCB Pharma, Berkshire, UK.
¹² Translational Research and Precision Medicine, Genmab BV, Utrecht, the Netherlands.
¹³ Institut Pasteur, Université de Paris, Unit of Antibodies in Therapy and Pathology, Paris, France.
¹⁴ Department of Preventive Medicine and Department of Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
¹⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
¹⁶ Service de Médecine Interne, Centre de Référence des Cytopénies Auto-immunes de l'adulte, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est Créteil, Créteil, France.
¹⁷ Moderna Inc., Cambridge, Massachusetts, USA.
¹⁸ Department of Pathology, Miller School of Medicine, University of Miami, Miami, Florida, USA.
¹⁹ Immunology Unit, Institut Pasteur du Cambodge, The Pasteur Network, Phnom Penh, Cambodia.
²⁰ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Invenra, Inc, Madison, Wisconsin, USA.
²² F-star Therapeutics Ltd., Cambridge, UK.
²³ IGM Biosciences, Inc., Mountainview, California, USA.
²⁴ Lava Therapeutics, Utrecht, the Netherlands.
²⁵ Emerging Infectious Diseases Branch, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
²⁶ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
²⁷ Computational Biology, Adimab, Palo Alto, California, USA.
²⁸ Department of Molecular Genetics, Donnelly Centre for Cellular and Biomolecular Research, Toronto, Ontario, Canada.
²⁹ Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
³⁰ Department of Statistics, University of Oxford, Oxford, UK.
³¹ Generate Biomedicines, Somerville, Massachusetts, USA.
³² Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³³ Merus N.V., Utrecht, the Netherlands.
³⁴ Regeneron Pharmaceuticals, Tarrytown, New York, USA.
³⁵ Mabylon AG, Schlieren, Switzerland.
³⁶ University of Oxford, Oxford, UK.

PMID: 36382536
PMCID: PMC10103175
DOI: 10.1111/nyas.14915

Abstract

Therapeutic antibodies have broad indications across diverse disease states, such as oncology, autoimmune diseases, and infectious diseases. New research continues to identify antibodies with therapeutic potential as well as methods to improve upon endogenous antibodies and to design antibodies de novo. On April 27-30, 2022, experts in antibody research across academia and industry met for the Keystone symposium "Antibodies as Drugs" to present the state-of-the-art in antibody therapeutics, repertoires and deep learning, bispecific antibodies, and engineering.

Keywords: SARS-CoV-2; allergies; antibodies; antibody design; bispecific antibodies; therapeutic antibodies.

PubMed Disclaimer

Conflict of interest statement

COMPETING INTERESTS

N. Pengo is an employee of Mabylon AG. Outside of the work described herein, P. Bruhns received consulting fees from Regeneron Pharmaceuticals.

Figures

**FIGURE 1**
(A) Format of a B-Body. C_H3 domains with mutations to drive heterodimerization replace one C_H1/C_L pair. (B) Nonoptimized production of several bispecific B-Body clones is 11 g/L. The final purified yield (also nonoptimized) was 5–6 g/L. (C) Treatment with the murine surrogate of a Treg SNIPER^™ cures 4/5 mice at the lowest dose of 0.4 mg/kg dosed once. Higher doses cured all mice.

See this image and copyright information in PMC

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Antibodies as drugs-a Keystone Symposia report

Affiliations

Antibodies as drugs-a Keystone Symposia report

Authors

Affiliations

Abstract

Conflict of interest statement

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