Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy

Claude Sportes, Rebecca R. Babb, Michael C. Krumlauf, Frances T. Hakim, Seth M. Steinberg, Catherine K. Chow, Margaret R. Brown, Thomas A. Fleisher, Pierre Noel, Irina Maric, Maryalice Stetler-Stevenson, Julie Engel, Renaud Buffet, Michel Morre, Robert J. Amato, Andrew Pecora, Crystal L. Mackall, Ronald E. Gress

Research output: Contribution to journalArticle

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Abstract

Purpose: Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans. Design: Subjects with incurable malignancy received rhIL-7 subcutaneously every other day for 2 weeks in a phase I interpatient dose escalation study (3, 10, 30, and 60 μg/kg/dose). The objectives were safety and dose-limiting toxicity determination, identification of a range of biologically active doses, and characterization of biological and, possibly, antitumor effects. Results: Mild to moderate constitutional symptoms, reversible spleen and lymph node enlargement, and marked increase in peripheral CD3 +, CD4+, and CD8+ lymphocytes were seen in a dose-dependent and age-independent manner in all subjects receiving ≥10 μg/kg/dose, resulting in a rejuvenated circulating T-cell profile, resembling that seen earlier in life. In some subjects, rhIL-7 induced in the bone marrow a marked, transient polyclonal proliferation of pre-B cells showing a spectrum of maturation as well as an increase in circulating transitional B cells. Conclusion: This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications.

Original languageEnglish (US)
Pages (from-to)727-735
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number2
DOIs
StatePublished - Jan 15 2010

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Interleukin-7
B-Lymphoid Precursor Cells
Neoplasms
Human Activities
T-Lymphocytes
Hematopoiesis
Immunotherapy
Stem Cells
Spleen
Lymph Nodes
Bone Marrow
HIV
Lymphocytes
Cytokines
Transplants
Safety
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sportes, C., Babb, R. R., Krumlauf, M. C., Hakim, F. T., Steinberg, S. M., Chow, C. K., ... Gress, R. E. (2010). Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clinical Cancer Research, 16(2), 727-735. https://doi.org/10.1158/1078-0432.CCR-09-1303

Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. / Sportes, Claude; Babb, Rebecca R.; Krumlauf, Michael C.; Hakim, Frances T.; Steinberg, Seth M.; Chow, Catherine K.; Brown, Margaret R.; Fleisher, Thomas A.; Noel, Pierre; Maric, Irina; Stetler-Stevenson, Maryalice; Engel, Julie; Buffet, Renaud; Morre, Michel; Amato, Robert J.; Pecora, Andrew; Mackall, Crystal L.; Gress, Ronald E.

In: Clinical Cancer Research, Vol. 16, No. 2, 15.01.2010, p. 727-735.

Research output: Contribution to journalArticle

Sportes, C, Babb, RR, Krumlauf, MC, Hakim, FT, Steinberg, SM, Chow, CK, Brown, MR, Fleisher, TA, Noel, P, Maric, I, Stetler-Stevenson, M, Engel, J, Buffet, R, Morre, M, Amato, RJ, Pecora, A, Mackall, CL & Gress, RE 2010, 'Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy', Clinical Cancer Research, vol. 16, no. 2, pp. 727-735. https://doi.org/10.1158/1078-0432.CCR-09-1303
Sportes, Claude ; Babb, Rebecca R. ; Krumlauf, Michael C. ; Hakim, Frances T. ; Steinberg, Seth M. ; Chow, Catherine K. ; Brown, Margaret R. ; Fleisher, Thomas A. ; Noel, Pierre ; Maric, Irina ; Stetler-Stevenson, Maryalice ; Engel, Julie ; Buffet, Renaud ; Morre, Michel ; Amato, Robert J. ; Pecora, Andrew ; Mackall, Crystal L. ; Gress, Ronald E. / Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 2. pp. 727-735.
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AU - Babb, Rebecca R.

AU - Krumlauf, Michael C.

AU - Hakim, Frances T.

AU - Steinberg, Seth M.

AU - Chow, Catherine K.

AU - Brown, Margaret R.

AU - Fleisher, Thomas A.

AU - Noel, Pierre

AU - Maric, Irina

AU - Stetler-Stevenson, Maryalice

AU - Engel, Julie

AU - Buffet, Renaud

AU - Morre, Michel

AU - Amato, Robert J.

AU - Pecora, Andrew

AU - Mackall, Crystal L.

AU - Gress, Ronald E.

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N2 - Purpose: Interleukin-7 (IL-7) has critical and nonredundant roles in T-cell development, hematopoiesis, and postdevelopmental immune functions as a prototypic homeostatic cytokine. Based on a large body of preclinical evidence, it may have multiple therapeutic applications in immunodeficiency states, either physiologic (immunosenescence), pathologic (HIV), or iatrogenic (postchemotherapy and posthematopoietic stem cell transplant), and may have roles in immune reconstitution or enhancement of immunotherapy. We report here on the toxicity and biological activity of recombinant human IL-7 (rhIL-7) in humans. Design: Subjects with incurable malignancy received rhIL-7 subcutaneously every other day for 2 weeks in a phase I interpatient dose escalation study (3, 10, 30, and 60 μg/kg/dose). The objectives were safety and dose-limiting toxicity determination, identification of a range of biologically active doses, and characterization of biological and, possibly, antitumor effects. Results: Mild to moderate constitutional symptoms, reversible spleen and lymph node enlargement, and marked increase in peripheral CD3 +, CD4+, and CD8+ lymphocytes were seen in a dose-dependent and age-independent manner in all subjects receiving ≥10 μg/kg/dose, resulting in a rejuvenated circulating T-cell profile, resembling that seen earlier in life. In some subjects, rhIL-7 induced in the bone marrow a marked, transient polyclonal proliferation of pre-B cells showing a spectrum of maturation as well as an increase in circulating transitional B cells. Conclusion: This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications.

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