# Core B:  Antibody/Ig fusion protein core

> **NIH NIH P01** · HARVARD MEDICAL SCHOOL · 2020 · $308,587

## Abstract

Core B, the Antibody / Ig Fusion Core, provides an important means by which the PPG will achieve its goals of
understanding the immune response in tolerance, autoimmunity and infection. Core B will coordinate the use of
mAb and Ig fusion proteins to enable the study of the roles of the PD-1 and other coinhibitory pathways in
regulating immune responses during acute and chronic infection, chronic graft versus host disease (cGVHD),
and autoimmunity. To achieve these goals Core B has the following aims:
Aim 1: To maintain and produce existing and newly generated mAbs and Ig fusion proteins for PPG
investigators.
An extensive set of mAbs and fusion proteins against coinhibitory molecules has been generated in previous
cycles of this PPG and these will continue to be produced as well as characterized for additional activities and
uses.
Aim 2: To generate novel monoclonal antibodies and Ig fusion proteins to study the function and
expression of coinhibitory receptors and ligands.
CD112R and CD101 are newly identified co-inhibitory molecules that impact T cell exhaustion and the PD-1
pathway. Core B will generate novel antibodies that will facilitate analysis of the function and expression of
coinhibitory molecules particularly CD112R, CD101 and PD-1/PD-L pathway members as well as other
coinhibitory pathways. These include novel mouse anti-mouse antibodies made in knockout mice that see
novel epitopes and facilitate long-term treatment of mice without anti-antibody responses. These novel mouse
anti-mouse mAbs will also be made as recombinant mAbs with mutated Fc to eliminate effects due to cell
depletion or FcR signaling. This best models PD-1 mAbs used in clinical trials. Tyrosine phosphorylation of the
PD-1 cytoplasmic domain mediates PD-1 biological activity. Core B will make phospho PD-1 ITIM mAbs and
together with our phospho PD-1 ITSM mAb, use these to monitor PD-1 signaling and understand the roles of
the PD-1 ITSM and ITIM motifs in regulating different T cell subsets in different disease states. The production
of these critical reagents by a core not only will be time and cost efficient, but also provide standardized
reagents that will facilitate comparison of data by investigators in this PPG. Core B will work closely with all
PPG investigators, providing mAbs and Ig fusion proteins and identifying new needs. These reagents will allow
PPG investigators to develop a comprehensive understanding of the roles of positive and negative second
signals in modulating T cell activation, tolerance and exhaustion.

## Key facts

- **NIH application ID:** 9996458
- **Project number:** 5P01AI056299-17
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Gordon James Freeman
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $308,587
- **Award type:** 5
- **Project period:** 2003-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996458

## Citation

> US National Institutes of Health, RePORTER application 9996458, Core B:  Antibody/Ig fusion protein core (5P01AI056299-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9996458. Licensed CC0.

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