# Molecular mechanisms of antibody-mediated immunotherapies

> **NIH NIH R35** · ROCKEFELLER UNIVERSITY · 2022 · $1,017,000

## Abstract

ABSTRACT
Our studies over the past two decades have focused on clarifying the mechanisms by which anti-tumor
immunotherapies elicit their therapeutic effects. As a result of our studies, the importance of Fc-FcγR mediated
effector pathways for the elimination of tumors has been elucidated, resulting in the optimization of these
interactions in second-generation anti-tumor immunotherapeutics with improved clinical activity. One of the
therapies developed as part of our previously funded NCI studies is now being tested across three clinical trials
with early evidence of promising activity. While strategies improving antibody-based therapeutics through Fc
engineering have resulted in more effective anti-tumor antibodies (Abs) with significantly improved survival, the
long-term goal of immunotherapy is to develop therapeutic strategies that will elicit memory responses and
effectively eliminate recurrences, resulting in improvements in overall survival. This current proposal aims to
mechanistically investigate general strategies to accomplish this goal by focusing on 1) inducing tumor
vaccination using anti-tumor monoclonal Abs (mAbs), 2) define the mechanisms by which agonistic and
antagonistic immunomodulatory mAbs enhance anti-tumor vaccination, and 3) explore how the tumor
microenvironment may be manipulated to improve these immunotherapeutic strategies. Our preliminary results
have indicated that anti-tumor Abs can elicit long-term cellular memory responses when appropriate Fc-FcγR
interactions are integrated into these Abs. Manipulating both the cellular effector responses and the tumor
microenvironment through the use of Fc-optimized immunomodulatory Abs can further augment these
pathways and result in long-term memory responses.

## Key facts

- **NIH application ID:** 10518790
- **Project number:** 2R35CA196620-08
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** JEFFREY Victor RAVETCH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,017,000
- **Award type:** 2
- **Project period:** 2016-04-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518790

## Citation

> US National Institutes of Health, RePORTER application 10518790, Molecular mechanisms of antibody-mediated immunotherapies (2R35CA196620-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10518790. Licensed CC0.

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