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Engineering and Technology

Biomedical & Chemical Engineering Candidate Seminar: Larry Dooling

January 20, 2023 at 10:00am11:00am EST

Bowne Hall, 414

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The Department of Biomedical & Chemical Engineering is pleased to welcome faculty candidate Dr. Larry Dooling from the University of Pennsylvania in presenting his candidate seminar: “Cooperative Phagocytosis Underlies Macrophage Immunotherapy of Solid Tumors”

Abstract

Macrophages are abundant in many solid tumors and typically associate with poor prognosis. However, macrophage aggregates in tumor nests have been reported to be beneficial in some types of human tumors even though this spatial arrangement limits contacts with cancer cells. Here, by maximizing phagocytic activity through tumor cell opsonization with a monoclonal antibody and deep disruption of the CD47:SIRPα macrophage immune checkpoint, we discover cooperative phagocytosis by macrophage clusters in rapidly growing “immuno-tumoroid” models. The net growth of cancer cells in immuno-tumoroids fits the calculus of proliferation opposed by cooperative (i.e., Hill-like) phagocytosis. Rheological measurements confirm the cohesiveness of cancer cell targets and provide a basis for understanding how phagocytic macrophages must disrupt cohesive forces between target cells. The same therapeutic approaches along with systemic delivery of engineered macrophages to maximize effector cell numbers suppress tumor growth in vivo and durably protect some mice from re-challenge and metastasis. Surviving mice produce anti-cancer IgG’s that are tumor-specific but recognize a broad repertoire of epitopes. The durable anti-tumor responses here illustrate unexpected advantages of increased macrophage density and clustering in tumors in combination with opsonizing antibodies and checkpoint blockade that maximizes phagocytic activity.

 

For more information, contact Prof. Zhen Ma at zma112@syr.edu

This event was published on January 6, 2023.


Event Details