ATAK™ Development Timeline

Over 120 years of research has resulted in the emergence of Myeloid Therapeutics & its platform technologies

1882

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Élie Metchnikof discovers Phagocytes (myeloid cells)

His theory, that certain white blood cells (myeloid cells) could engulf and destroy harmful bodies such as bacteria, met with skepticism from leading specialists including Louis Pasteur, Behring and others. His major supporter was Rudolf Virchow, who published his research in his Archiv für pathologische Anatomie und Physiologie und für klinische Medizin (now called the Virchows Archiv).[12] His discovery of these phagocytes  ultimately won him the Nobel Prize in 1908[7].

1902

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Almroth Wright

Almroth Wright subsequently emphasized the importance of phagocytes (polymorphonuclear leukocytes, initially described as macrophages) and of plasma/serum-dependent opsonisation (from the Greek, to prepare for eating) in resistance to infection.

1968

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Ralph van Furth & Zanvill Cohn

Ralph van Furth & Zanvill Cohn describe a group of leukocytes that shared phenotypic features (e.g., a single nucleus) and biological functions (e.g., phagocytosis). In spite of the subsequent improved characterization of diverse cells arising from common progenitors and sharing differentiation antigen markers, there is still considerable confusion in categorizing myeloid cell sub-populations.

Current - Recent

 

Early Research

1976

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Siamon Gordon

Scientific Advisory Board

Siamon Gordon identified the pan-macrophage marker F4/80. Subsequent studies led to the identification of various scavenger receptors and the cloning of the pattern recognition receptor, Dectin-1. 

1983

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Alberto Motavani

Scientific Advisory Board

Alberto Motavani is the first to identify monocyte chemoattractant protein (CCL2) as a primary chemokine for recruiting myeloid cells.

1989

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Charles Janeway

Janeway predicted that activation of the adaptive immune response is controlled by the more ancient innate immune system. He proposed a general theory of innate immune recognition (pattern recognition theory) and suggested the principles of innate control of adaptive immunity.[4] These predictions have been confirmed in subsequent years and now form the conceptual framework for the current understanding of the innate immune system and the links between innate and adaptive immunity.[5]

Legacies of 1989 Research

 

ADVANCES IN CELL ENGINEERING & CHIMERIC ANTIGEN RECEPTORS

1989

The first generation of  Chimeric Antigen Receptors are described

Gross and colleagues designed and detailed the construction process of what later became known as first-generation CAR-T.  Gross et al engineered genetically modified human cytotoxic T cells in which expression of chimeric surface receptors was promoted, conferring antibody-like specificity upon the cells.

1998

Neutrophil expression with T cell CAR is shown 

Antigen-Specific Cytolysis by Neutrophils and NK Cells Expressing Chimeric Immune Receptors Bearing ζ or γ Signaling Domains.

https://www.jimmunol.org/content/161/1/375

2006

Human myeloid cell expression of first generation anti-CEA CAR T cell 

Human myeloid cell expression of first generation anti-CEA CAR T cell construction using adenovirus (Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumor cells in vitro and in vivo Gene Therapy volume 13, pages 602–610 (2006). 

https://www.nature.com/gt/

2019

HER2 CAR receptors are expressed on macrophages 

Chimeric antigen receptor macrophage therapy for breast tumors mediated by targeting the tumor extracellular matrix.  (Br J Cancer. 2019 Nov; 121(10):837-845. doi: 10.1038/s41416-019-0578-3. Epub 2019 Oct 1).

Myeloid Cell Trafficking

 

2008

Nicholas King

Scientific Advisory Board

The role of myeloid cells in viral infections and the finding that myeloid cells are recruited to sites of infection and differentiate into numerous cell types.

2014

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Miriam Merad

Scientific Advisory Board

The migration of myeloid cells into tumors.

2018-2020

 

2018

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Ronald Vale

Founder

Vale and his team show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, they showed that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%.

2019

MYELOID THERAPEUTICS IS FORMED 

April 2019, the first meeting of the Myeloid SAB is convened and the company’s initiatives forwarded in earnest and haste. 

2019

Michael Dee Gunn

Scientific Advisory Board

Duke University

Dr. Gunn discovers the potential for myeloid cells to activate t cell responses. The recent focus of his work has been on determining how dendritic cells and other myeloid cells regulate immune responses and contribute to disease pathogenesis. 

2020

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Siddhartha Mukherjee

Founder, Advisory Board Chair

Siddhartha Mukherjee is the author of The Emperor of All Maladies: A Biography of Cancer, winner of the 2011 Pulitzer Prize in general nonfiction, and The Laws of Medicine. He is the editor of Best Science Writing 2013.

Siddhartha Mukherjee’s THE GENE: An Intimate History is his latest work – the story of the quest to decipher the master-code of instructions that makes and defines humans, that governs our form, function, and fate and determines the future of our children.

 

© 2020,   Myeloid Therapeutics.  All rights reserved.

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