Molecular characterization and modeling efficient antibody effector function
Project Number1R01AI186995-01
Contact PI/Project LeaderACKERMAN, MARGARET E
Awardee OrganizationDARTMOUTH COLLEGE
Description
Abstract Text
ABSTRACT
Antibody effector functions represent a nexus linking innate and adaptive arms of the immune system and also
have direct clinical implications for antibody therapeutics and antibody-mediated pathologies. However, the
potency of Ab-dependent effector responses depends on numerous antigen, antibody and effector cell
properties. Variable antigen expression levels, accessibility and context on different targets influence not only
Ab binding but also the ability of the effector cell to kill or engulf its target. Based on the extensive diversity of
natural and engineered antibody forms and formats, both B cells and immunologists can engineer antibodies
with different flexibility, affinity, and avidity to manipulate the effector response. The complexity of these
interactions makes in vivo experimental testing of all combinations impractical, but the significance of these
activities to antibody-based protection and pathology and the opportunity to design agents with a high
probability of success once the fundamental cellular presentation mechanisms are understood makes
quantitative analysis of this complex biological landscape of high significance. This proposal will elucidate our
basic understanding of the cellular mechanisms that can drive advancements in the practical development of
immune therapeutics and the parameters by which both B cells and effectors can drive variation in the
outcome of antibody recognition. Overall, this work seeks to distill quantitative relationships between antigen,
antibody, and effector biology to establish “rules” that enable the generation of antibody design criteria that
encapsulate key landmarks in the antibody effector function landscape and enable robust prediction of this
critical aspect of antibody activity.
Public Health Relevance Statement
NARRATIVE
A subset of antibodies can link natural killer (NK) cells and other effector cell types with pathogenic targets to
activate their innate immune effector function capacities. We will experimentally characterize features that
endow antibodies with the capacity to trigger potent ADCC and phagocytosis, working towards establishing
general rules that can guide antibody immunotherapies.
National Institute of Allergy and Infectious Diseases
CFDA Code
855
DUNS Number
041027822
UEI
EB8ASJBCFER9
Project Start Date
16-December-2024
Project End Date
30-November-2029
Budget Start Date
16-December-2024
Budget End Date
30-November-2025
Project Funding Information for 2025
Total Funding
$442,024
Direct Costs
$280,379
Indirect Costs
$161,645
Year
Funding IC
FY Total Cost by IC
2025
National Institute of Allergy and Infectious Diseases
$442,024
Year
Funding IC
FY Total Cost by IC
Sub Projects
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Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
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Clinical Studies
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