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, Eric C. Vonderheid

Research output: Contribution to journalArticlepeer-review

238 Scopus citations


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 (rhlL-12) where patients received either 50, 100, or 300 ng/kg rhlL-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 I 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 rhlL-12 on this regimen were minor and limited and included low- grade fever and headache. One patient discontinued rhlL-12 at week 6 because of depression. These results suggest that rhlL-12 may augment antitumor cytotoxic T-cell responses and may represent a potent and well-tolerated therapeutic agent for CTCL.

Original languageEnglish (US)
Pages (from-to)902-908
Number of pages7
Issue number3
StatePublished - Aug 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Hematology


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