# A Drug Delivery Strategy for Targeted Therapy of Chronic Lymphocytic Leukemia

> **NIH NIH R01** · SCRIPPS FLORIDA · 2020 · $575,010

## Abstract

This project generates, validates, and delivers novel antibody-drug conjugates (ADCs) that are designed to
selectively and potently eradicate chronic lymphocytic leukemia (CLL), the most common leukemia in the U.S.,
without affecting healthy cells and tissues. CLL is an indolent yet incurable B-cell malignancy that afflicts more
than 150,000 men and women and causes more than 4,500 deaths per year in the U.S. alone. There are
currently no treatment options for CLL that allow for selective targeting of malignant B cells and that spare
healthy B cells and other healthy cells and tissues. With this Premise, the project is built on the Hypothesis
that the Fcµ receptor FCMR, on its own or in combination with other selectively expressed CLL cell surface
antigens, can mediate rapid and effective cellular entry of cytotoxic drugs for potent and specific therapeutic
intervention. Two independent Specific Aims will be pursued to rigorously test this hypothesis. In Aim 1, a
series of molecularly defined ADCs will be generated that deliver and release a highly cytotoxic tubulin inhibitor
and a highly cytotoxic DNA-targeting drug, on their own or in combination, via the FCMR internalization and
trafficking pathway. These ADCs will be based on the selenomab-drug conjugate platform which utilizes an
engineered selenocysteine residue for site-specific drug conjugation. By extensive validation in vitro, ex vivo,
and in vivo, a panel of FCMR-targeting selenomab-drug conjugates will be assessed for their stability,
specificity, potency, toxicity, and pharmacokinetics. Aim 2 builds on a novel dual variable domain (DVD)-IgG1-
based ADC platform that utilizes a unique reactive lysine residue for site-specific drug conjugation. DVD-IgM-
based ADCs that can simultaneously engage FCMR and a second CLL cell surface antigen will be built and
extensively validated. In addition to a highly modular research strategy that systematically compares different
targets, different antibodies, different antibody formats, different linkers, and different drugs, the ex vivo and in
vivo experiments in both Specific Aims will be based on peripheral blood mononuclear cells from male and
female CLL patients rather than on cell lines to collectively achieve Robust and Unbiased Results toward
delivering a candidate for advanced preclinical investigations and eventual clinical translation. Throughout this
campaign, conceptually novel biological and chemical components with broad applicability to next-generation
ADCs for cancer therapy will be developed.

## Key facts

- **NIH application ID:** 9898332
- **Project number:** 5R01CA174844-06
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** CHRISTOPH RADER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $575,010
- **Award type:** 5
- **Project period:** 2013-06-12 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898332

## Citation

> US National Institutes of Health, RePORTER application 9898332, A Drug Delivery Strategy for Targeted Therapy of Chronic Lymphocytic Leukemia (5R01CA174844-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898332. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*