Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity

Daniela Montagna, Eric Yvon, Valeria Calcaterra, Patrizia Comoli, Franco Locatelli, Rita Maccario, Alain Fisher, Marina Cavazzana-Calvo

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

The success of bone marrow transplantation (BMT) from HLA-disparate donors depends on the development of new strategies able, on one hand, to efficiently prevent graft-versus-host disease (GVHD) and, on the other hand, to protect leukemic patients from relapse and infections. Using an immunotoxin (IT) directed against the α chain (p55) of the human interleukin-2 receptor (RFT5-SMPT-dgA), we previously showed that it is possible to kill mature T cells activated against a specific HLA complex by a one-way mixed lymphocyte culture (MLC). The present study was performed to investigate whether this protocol of allodepletion affects the capacity of residual T cells to display antileukemia and antiviral activity evaluated by limiting dilution assays (LDA), measuring the frequency of cytotoxic T- lymphocyte precursors (CTLp) directed against autologous leukemic blasts (LB) and cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia activity was evaluated in peripheral blood mononuclear cells (PBMC) of 3 patients treated for acute myeloid leukemia who had developed a high frequency of LB-reactive CTLp after either autologous or allogeneic BMT. Results demonstrate that (1) depletion with RFT5-SMPT-dgA efficiently inhibited MLC; (2) fresh PBMC of patients yielded a high frequency of LB-reactive CTLp comparable to that of the mock-treated PBMC; and (3) effector cells obtained after allodepletion fully retained the capacity to lyse pretransplant LB. By contrast, the frequency of CTLp directed against patient's pretransplant BM remission cells was always undetectable. Data obtained in 4 healthy donors showed that specifically allodepleted T cells recognized and killed autologous CMV-infected fibroblasts and autologous EBV-B-lymphoblastoid cell lines. In conclusion, our data indicate that allodepletion using RFT5-SMPT-dgA efficiently removed alloreactive cells, while sparing in vitro antileukemic and antiviral cytotoxic responses.

Original languageEnglish
Pages (from-to)3550-3557
Number of pages8
JournalBlood
Volume93
Issue number10
Publication statusPublished - May 15 1999

Fingerprint

Immunotoxins
T-cells
Interleukin-2 Receptors
Cytotoxic T-Lymphocytes
Antiviral Agents
T-Lymphocytes
Blood Cells
Cytomegalovirus
Bone Marrow Transplantation
Human Herpesvirus 4
Cells
Tissue Donors
Lymphocytes
Blood
Viruses
Cell culture
Homologous Transplantation
Graft vs Host Disease
Acute Myeloid Leukemia
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity. / Montagna, Daniela; Yvon, Eric; Calcaterra, Valeria; Comoli, Patrizia; Locatelli, Franco; Maccario, Rita; Fisher, Alain; Cavazzana-Calvo, Marina.

In: Blood, Vol. 93, No. 10, 15.05.1999, p. 3550-3557.

Research output: Contribution to journalArticle

@article{07263abc488a45f7bd5e825d0179ff48,
title = "Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity",
abstract = "The success of bone marrow transplantation (BMT) from HLA-disparate donors depends on the development of new strategies able, on one hand, to efficiently prevent graft-versus-host disease (GVHD) and, on the other hand, to protect leukemic patients from relapse and infections. Using an immunotoxin (IT) directed against the α chain (p55) of the human interleukin-2 receptor (RFT5-SMPT-dgA), we previously showed that it is possible to kill mature T cells activated against a specific HLA complex by a one-way mixed lymphocyte culture (MLC). The present study was performed to investigate whether this protocol of allodepletion affects the capacity of residual T cells to display antileukemia and antiviral activity evaluated by limiting dilution assays (LDA), measuring the frequency of cytotoxic T- lymphocyte precursors (CTLp) directed against autologous leukemic blasts (LB) and cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia activity was evaluated in peripheral blood mononuclear cells (PBMC) of 3 patients treated for acute myeloid leukemia who had developed a high frequency of LB-reactive CTLp after either autologous or allogeneic BMT. Results demonstrate that (1) depletion with RFT5-SMPT-dgA efficiently inhibited MLC; (2) fresh PBMC of patients yielded a high frequency of LB-reactive CTLp comparable to that of the mock-treated PBMC; and (3) effector cells obtained after allodepletion fully retained the capacity to lyse pretransplant LB. By contrast, the frequency of CTLp directed against patient's pretransplant BM remission cells was always undetectable. Data obtained in 4 healthy donors showed that specifically allodepleted T cells recognized and killed autologous CMV-infected fibroblasts and autologous EBV-B-lymphoblastoid cell lines. In conclusion, our data indicate that allodepletion using RFT5-SMPT-dgA efficiently removed alloreactive cells, while sparing in vitro antileukemic and antiviral cytotoxic responses.",
author = "Daniela Montagna and Eric Yvon and Valeria Calcaterra and Patrizia Comoli and Franco Locatelli and Rita Maccario and Alain Fisher and Marina Cavazzana-Calvo",
year = "1999",
month = "5",
day = "15",
language = "English",
volume = "93",
pages = "3550--3557",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity

AU - Montagna, Daniela

AU - Yvon, Eric

AU - Calcaterra, Valeria

AU - Comoli, Patrizia

AU - Locatelli, Franco

AU - Maccario, Rita

AU - Fisher, Alain

AU - Cavazzana-Calvo, Marina

PY - 1999/5/15

Y1 - 1999/5/15

N2 - The success of bone marrow transplantation (BMT) from HLA-disparate donors depends on the development of new strategies able, on one hand, to efficiently prevent graft-versus-host disease (GVHD) and, on the other hand, to protect leukemic patients from relapse and infections. Using an immunotoxin (IT) directed against the α chain (p55) of the human interleukin-2 receptor (RFT5-SMPT-dgA), we previously showed that it is possible to kill mature T cells activated against a specific HLA complex by a one-way mixed lymphocyte culture (MLC). The present study was performed to investigate whether this protocol of allodepletion affects the capacity of residual T cells to display antileukemia and antiviral activity evaluated by limiting dilution assays (LDA), measuring the frequency of cytotoxic T- lymphocyte precursors (CTLp) directed against autologous leukemic blasts (LB) and cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia activity was evaluated in peripheral blood mononuclear cells (PBMC) of 3 patients treated for acute myeloid leukemia who had developed a high frequency of LB-reactive CTLp after either autologous or allogeneic BMT. Results demonstrate that (1) depletion with RFT5-SMPT-dgA efficiently inhibited MLC; (2) fresh PBMC of patients yielded a high frequency of LB-reactive CTLp comparable to that of the mock-treated PBMC; and (3) effector cells obtained after allodepletion fully retained the capacity to lyse pretransplant LB. By contrast, the frequency of CTLp directed against patient's pretransplant BM remission cells was always undetectable. Data obtained in 4 healthy donors showed that specifically allodepleted T cells recognized and killed autologous CMV-infected fibroblasts and autologous EBV-B-lymphoblastoid cell lines. In conclusion, our data indicate that allodepletion using RFT5-SMPT-dgA efficiently removed alloreactive cells, while sparing in vitro antileukemic and antiviral cytotoxic responses.

AB - The success of bone marrow transplantation (BMT) from HLA-disparate donors depends on the development of new strategies able, on one hand, to efficiently prevent graft-versus-host disease (GVHD) and, on the other hand, to protect leukemic patients from relapse and infections. Using an immunotoxin (IT) directed against the α chain (p55) of the human interleukin-2 receptor (RFT5-SMPT-dgA), we previously showed that it is possible to kill mature T cells activated against a specific HLA complex by a one-way mixed lymphocyte culture (MLC). The present study was performed to investigate whether this protocol of allodepletion affects the capacity of residual T cells to display antileukemia and antiviral activity evaluated by limiting dilution assays (LDA), measuring the frequency of cytotoxic T- lymphocyte precursors (CTLp) directed against autologous leukemic blasts (LB) and cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-infected target cells. Antileukemia activity was evaluated in peripheral blood mononuclear cells (PBMC) of 3 patients treated for acute myeloid leukemia who had developed a high frequency of LB-reactive CTLp after either autologous or allogeneic BMT. Results demonstrate that (1) depletion with RFT5-SMPT-dgA efficiently inhibited MLC; (2) fresh PBMC of patients yielded a high frequency of LB-reactive CTLp comparable to that of the mock-treated PBMC; and (3) effector cells obtained after allodepletion fully retained the capacity to lyse pretransplant LB. By contrast, the frequency of CTLp directed against patient's pretransplant BM remission cells was always undetectable. Data obtained in 4 healthy donors showed that specifically allodepleted T cells recognized and killed autologous CMV-infected fibroblasts and autologous EBV-B-lymphoblastoid cell lines. In conclusion, our data indicate that allodepletion using RFT5-SMPT-dgA efficiently removed alloreactive cells, while sparing in vitro antileukemic and antiviral cytotoxic responses.

UR - http://www.scopus.com/inward/record.url?scp=0033562349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033562349&partnerID=8YFLogxK

M3 - Article

VL - 93

SP - 3550

EP - 3557

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -