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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 902-908
Interleukin-12 Therapy of Cutaneous T-Cell Lymphoma Induces Lesion
Regression and Cytotoxic T-Cell Responses
Alain H. Rook,
Gary S. Wood,
Elisa K. Yoo,
Rosalie Elenitsas,
David M.F. Kao,
Matthew L. Sherman,
William K. Witmer,
Kenneth A. Rockwell,
Ryan B. Shane,
Stuart R. Lessin, and
Eric C. Vonderheid
From the Department of Dermatology, University of Pennsylvania School
of Medicine, Philadelphia, PA; the Department of Dermatology, Case
Western Reserve School of Medicine, Cleveland, OH; Genetics Institute,
Inc, Cambridge, MA; Investigational Pharmacy, Hospital of the
University of Pennsylvania, Philadelphia, PA; and the Department of
Dermatology, Allegheny University School of Medicine, Philadelphia, PA.
Progression of cutaneous T-cell lymphoma (CTCL) is associated with
profound defects in cell-mediated immunity and depressed production of
cytokines, which support cell-mediated immunity. Because we have
observed marked defects in interleukin-12 (IL-12) production in CTCL
and because IL-12 is critical for antitumor cytotoxic T-cell responses,
we initiated a phase I dose escalation trial with recombinant human
IL-12 (rhIL-12) where patients received either 50, 100, or 300 ng/kg
rhIL-12 twice weekly subcutaneously or intralesionally for up to 24 weeks. Ten patients were entered: 5 with extensive plaque, 3 with
Sezary syndrome, and 2 with extensive tumors with large cell
transformation. One patient with Sezary syndrome dropped out after 1 week for personal reasons. Subcutaneous dosing resulted in complete
responses (CR) in 2 of 5 plaque and partial responses (PR) in 2 of 5 plaque, and 1 of 2 Sezary syndrome (overall response rate
CR+PR 5 of 9, 56%). A minor response also occurred in 1 of 5 plaque patients. Intralesional dosing resulted in individual tumor
regression in 2 of 2 patients. Biopsy of regressing lesions showed a
significant decrease in the density of the infiltrate in all cases and
complete resolution of the infiltrate among those with clinical lesion
resolution. An increase in numbers of CD8-positive and/or
TIA-1-positive T cells were observed on
immunohistochemical analysis of skin biopsy specimens obtained from
regressing skin lesions. Adverse effects of rhIL-12 on this regimen
were minor and limited and included low-grade fever and headache. One
patient discontinued rhIL-12 at week 6 because of depression. These
results suggest that rhIL-12 may augment antitumor cytotoxic T-cell
responses and may represent a potent and well-tolerated therapeutic
agent for CTCL.
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