Immunotherapy with low-dose interleukin-2: Rationale for prevention of immune-deficiency-associated cancer

Vijay P. Khatri, Robert A. Baiocchi, Zale P. Bernstein, Michael A. Caligiuri

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

PURPOSE: Congenital, acquired, and some iatrogenically induced immune deficiencies are characterized by an increased incidence of viral-associated cancers. Preclinical and clinical studies were conducted to understand the pathogenesis of immune-deficiency-associated cancer and its response to low- dose recombinant interleukin-2 (rIL-2) therapy, with the ultimate goal of applying this or other immune therapy in the treatment or prevention of immune-deficiency-associated lymphoma. METHODS: We have used the severe combined immune-deficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBL) from healthy Epstein-Barr virus seropositive donors to study the pathogenesis of malignant B-cell lymphoproliferative disease that commonly occurs in some immune-deficient patients. In this chimeric human (hu)-PBL-SCID mouse model, administration of daily low-dose rIL-2 interacts with murine natural killer cells and human CD8+ T cells to prevent the outgrowth of human Epstein-Barr virus lymphoproliferative disease. We have utilized the information gained from this chimeric mouse model to perform a phase I study of daily, subcutaneous, low-dose rIL-2 therapy in patients with both acquired immune deficiency syndrome (AIDS) and cancer. RESULTS: Plasma concentrations of rIL-2 were achieved in vive comparable to those seen in our hu-PBL-SCID model, in the absence of significant (grade 3) clinical toxicity or an increase in the plasma human immune deficiency virus (HIV) RNA level. Significant expansion in human cells, particularly the CD3-CD56(bright) natural killer cell subset, resulted after 6 weeks of therapy. Results of the hu-PBL-SCID mouse model and the phase I study have led to a national trial of low-dose rIL-2 therapy in AIDS-associated lymphoma. CONCLUSION: Daily low- dose rIL-2 therapy may be effective in treating or preventing AIDS- associated lymphoma without amplifying HIV replication.

Original languageEnglish (US)
JournalCancer Journal from Scientific American
Volume3
Issue numberSUPPL. 1
StatePublished - 1997
Externally publishedYes

Fingerprint

Immunotherapy
Interleukin-2
Neoplasms
Lymphocytes
Lymphoma
Acquired Immunodeficiency Syndrome
Human Herpesvirus 4
Natural Killer Cells
Therapeutics
RNA Viruses
Virus Diseases
Virus Replication
B-Lymphocytes
Tissue Donors
T-Lymphocytes
Incidence

Keywords

  • Acquired immune deficiency syndrome
  • Cytokine
  • Epstein-Barr virus
  • Immunodeficiency
  • Immunotherapy
  • Interleukin- 2
  • Lymphoma
  • Lymphoproliferative disorders

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunotherapy with low-dose interleukin-2 : Rationale for prevention of immune-deficiency-associated cancer. / Khatri, Vijay P.; Baiocchi, Robert A.; Bernstein, Zale P.; Caligiuri, Michael A.

In: Cancer Journal from Scientific American, Vol. 3, No. SUPPL. 1, 1997.

Research output: Contribution to journalArticle

Khatri, Vijay P. ; Baiocchi, Robert A. ; Bernstein, Zale P. ; Caligiuri, Michael A. / Immunotherapy with low-dose interleukin-2 : Rationale for prevention of immune-deficiency-associated cancer. In: Cancer Journal from Scientific American. 1997 ; Vol. 3, No. SUPPL. 1.
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AB - PURPOSE: Congenital, acquired, and some iatrogenically induced immune deficiencies are characterized by an increased incidence of viral-associated cancers. Preclinical and clinical studies were conducted to understand the pathogenesis of immune-deficiency-associated cancer and its response to low- dose recombinant interleukin-2 (rIL-2) therapy, with the ultimate goal of applying this or other immune therapy in the treatment or prevention of immune-deficiency-associated lymphoma. METHODS: We have used the severe combined immune-deficient (SCID) mouse engrafted with human peripheral blood lymphocytes (PBL) from healthy Epstein-Barr virus seropositive donors to study the pathogenesis of malignant B-cell lymphoproliferative disease that commonly occurs in some immune-deficient patients. In this chimeric human (hu)-PBL-SCID mouse model, administration of daily low-dose rIL-2 interacts with murine natural killer cells and human CD8+ T cells to prevent the outgrowth of human Epstein-Barr virus lymphoproliferative disease. We have utilized the information gained from this chimeric mouse model to perform a phase I study of daily, subcutaneous, low-dose rIL-2 therapy in patients with both acquired immune deficiency syndrome (AIDS) and cancer. RESULTS: Plasma concentrations of rIL-2 were achieved in vive comparable to those seen in our hu-PBL-SCID model, in the absence of significant (grade 3) clinical toxicity or an increase in the plasma human immune deficiency virus (HIV) RNA level. Significant expansion in human cells, particularly the CD3-CD56(bright) natural killer cell subset, resulted after 6 weeks of therapy. Results of the hu-PBL-SCID mouse model and the phase I study have led to a national trial of low-dose rIL-2 therapy in AIDS-associated lymphoma. CONCLUSION: Daily low- dose rIL-2 therapy may be effective in treating or preventing AIDS- associated lymphoma without amplifying HIV replication.

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