# IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATION

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 1991 · $153,269

## Abstract

Our purpose is to continue our basic and clinical research determining the
usefulness of immunotoxins (IT) in bone marrow transplantation (BMT).  It
will be utilized by the U. of Minnesota BMT Program to treat a variety of
otherwise lethal clinical disorders including acute and chronic leukemia.
In vivo use of IT - We will determine the usefulness of IT for systemic
therapy.  Because hemitoxins do not bind eukaryotic cells, we will link
them to monoclonal antibodies and test their potential for systemic
treatment of GVHD, for promotion of engraftment in allogeneic BMT, and for
more effective conditioning for BMT for leukemia.  We will also study IT
synthesized using recombinant toxins which may have the added in vivo
advantages of homogeneity, absence of carbohydrate residues that may effect
homing, and the capacity for genetic alteration.  Animal experiments will
also be used to study homing of IT to target cells, biodistribution,
pharmacokinetics, LD50, and damage to nontarget tissue.

Ex vivo use of IT - We will continue using IT to purge GVHD-causing cells
from normal donor marrow prior to allogeneic BMT.  We will optimize our
current approach using intact ricin IT by investigating various IT, e.g. T
cell subpopulation directed IT, and pan-T IT sparing NK cells.  We will
emphasize the use of various in vitro functional assays as models of in
vivo GVHD.  Efficacy of IT will be determined at the clonal level using a
variety of phenotypically and functionally different human T cell clones.
We will continue our ongoing clinical trials to determine which IT will be
the most efficacious for GVHD prophylaxis without concomitant engraftment
problems.  We will continue the clinical use of IT to purge residual
leukemia cells from BM prior to autologous BMT.  Choice of IT for purging T
or B-lineage leukemia will be based on IT activity against fresh leukemic
progenitor cells measured in novel colony assays and IT potency measured
using clonogenic assays by limiting dilution.

We will study ways of producing better IT.  We will determine the role of
differences in antibody subclass, FC portion, epitope recognition, and
affinity for the potency of IT.  Each IT will be evaluated in numerous
biological and biochemical assays for purity, specificity, and potency.
Our major goals are 1) to develop protocols for the in vivo use of IT in
the treatment of GVHD, leukemia, and graft promotion; 2) to optimize our in
vitro IT protocols that are currently undergoing clinical evaluation.

## Key facts

- **NIH application ID:** 3174313
- **Project number:** 5R01CA036725-08
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **SAM.gov UEI:** KABJZBBJ4B54
- **Principal Investigator:** Daniel A Vallera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $153,269
- **Award type:** 5
- **Project period:** 1984-01-01 → 1992-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174313

## Citation

> US National Institutes of Health, RePORTER application 3174313, IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATION (5R01CA036725-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174313. Licensed CC0.

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