IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity

Mary T. Litzinger, Romaine Fernando, Tyler J Curiel, Douglas W. Grosenbach, Jeffrey Schlom, Claudia Palena

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

CD4 +CD25 +Foxp3 + regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB 389IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigen-specific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox 1 day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine.

Original languageEnglish (US)
Pages (from-to)3192-3201
Number of pages10
JournalBlood
Volume110
Issue number9
DOIs
StatePublished - Nov 1 2007

Fingerprint

Immunotoxins
T-cells
Regulatory T-Lymphocytes
Cellular Immunity
Interleukin-2
Vaccines
T-Lymphocytes
Antigens
Vaccination
Scheduling
denileukin diftitox
Synthetic Vaccines
Histocompatibility Antigens Class II
Intraperitoneal Injections
Inbred C57BL Mouse
Immunity
Bone
Blood
Fusion reactions
Spleen

ASJC Scopus subject areas

  • Hematology

Cite this

IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. / Litzinger, Mary T.; Fernando, Romaine; Curiel, Tyler J; Grosenbach, Douglas W.; Schlom, Jeffrey; Palena, Claudia.

In: Blood, Vol. 110, No. 9, 01.11.2007, p. 3192-3201.

Research output: Contribution to journalArticle

Litzinger, Mary T. ; Fernando, Romaine ; Curiel, Tyler J ; Grosenbach, Douglas W. ; Schlom, Jeffrey ; Palena, Claudia. / IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. In: Blood. 2007 ; Vol. 110, No. 9. pp. 3192-3201.
@article{0f0ec4b324ed44e5af325274ff255339,
title = "IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity",
abstract = "CD4 +CD25 +Foxp3 + regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB 389IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigen-specific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox 1 day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine.",
author = "Litzinger, {Mary T.} and Romaine Fernando and Curiel, {Tyler J} and Grosenbach, {Douglas W.} and Jeffrey Schlom and Claudia Palena",
year = "2007",
month = "11",
day = "1",
doi = "10.1182/blood-2007-06-094615",
language = "English (US)",
volume = "110",
pages = "3192--3201",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity

AU - Litzinger, Mary T.

AU - Fernando, Romaine

AU - Curiel, Tyler J

AU - Grosenbach, Douglas W.

AU - Schlom, Jeffrey

AU - Palena, Claudia

PY - 2007/11/1

Y1 - 2007/11/1

N2 - CD4 +CD25 +Foxp3 + regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB 389IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigen-specific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox 1 day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine.

AB - CD4 +CD25 +Foxp3 + regulatory T (Treg) cells have been implicated in the lack of effective antitumor immunity. Denileukin diftitox (DAB 389IL-2), a fusion protein of interleukin 2 (IL-2) and diphtheria toxin, provides a means of targeting Treg cells. In this study, we examined (1) the effect of denileukin diftitox on the deletion of Treg cells in various lymphoid compartments and (2) the dose scheduling of denileukin diftitox in combination with a recombinant poxviral vaccine to enhance antigen-specific immune responses. Treg cells in spleen, peripheral blood, and bone marrow of normal C57BL/6 mice were variously reduced after a single intraperitoneal injection of denileukin diftitox; the reduction was evident within 24 hours and lasted approximately 10 days. Injection of denileukin diftitox 1 day before vaccination enhanced antigen-specific T-cell responses above levels induced by vaccination alone. These studies show for the first time in a murine model (1) the differential effects of denileukin diftitox on Treg cells in different cellular compartments, (2) the advantage of combining denileukin diftitox with a vaccine to enhance antigen-specific T-cell immune responses, (3) the lack of inhibition by denileukin diftitox of host immune responses directed against a live viral vector, and (4) the importance of dose scheduling of denileukin diftitox when used in combination with a vaccine.

UR - http://www.scopus.com/inward/record.url?scp=36148939150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36148939150&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-06-094615

DO - 10.1182/blood-2007-06-094615

M3 - Article

C2 - 17616639

AN - SCOPUS:36148939150

VL - 110

SP - 3192

EP - 3201

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -