# Molecular mechanisms of antibody-mediated immunotherapies

> **NIH NIH R35** · ROCKEFELLER UNIVERSITY · 2021 · $1,017,000

## Abstract

   
DESCRIPTION (provided by applicant): 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. While these strategies 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 that will effectively eliminate recurrences and thus result in long-term 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 in order to augment 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 augment these pathways to result in long-term memory responses.

## Key facts

- **NIH application ID:** 10135015
- **Project number:** 5R35CA196620-06
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** JEFFREY Victor RAVETCH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,017,000
- **Award type:** 5
- **Project period:** 2016-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135015

## Citation

> US National Institutes of Health, RePORTER application 10135015, Molecular mechanisms of antibody-mediated immunotherapies (5R35CA196620-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10135015. Licensed CC0.

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