Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses.
Publication/Presentation Date
8-1-1999
Abstract
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.
Volume
94
Issue
3
First Page
902
Last Page
908
ISSN
0006-4971
Published In/Presented At
Rook, A. H., Wood, G. S., Yoo, E. K., Elenitsas, R., Kao, D. M., Sherman, M. L., Witmer, W. K., Rockwell, K. A., Shane, R. B., Lessin, S. R., & Vonderheid, E. C. (1999). Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood, 94(3), 902–908.
Disciplines
Medicine and Health Sciences
PubMedID
10419880
Department(s)
Department of Medicine
Document Type
Article