Immunological Consequences of Interleukin 12 Administration after Autologous Stem Cell Transplantation

Abstract

Purpose:The purpose is to determine the immunological effects of recombinant human interleukin (rhIL)-12 therapy after autologous stem cell transplantation.Experimental Design: Twelve patients (8 non-Hodgkin's lymphoma, 2 Hodgkin's disease, and 2 plasma cell myeloma) were treated with rhIL-12 by bolus i.v. injection in doses of 30, 100, or 250 ng/kg starting at a median of 66 days posttransplant. Immunological assays were performed using serum and peripheral blood mononuclear cell (PBMC) samples obtained on study.Results: Dose-dependent increases in the total lymphocyte count occurred during rhIL-12 therapy. The absolute number of peripheral blood CD4 T cells increased up to 16.3-fold, CD8 T cells up to 20.5-fold, B cells up to 11-fold, and natural killer (NK) cells up to 12.3-fold during rhIL-12 administration and returned to pretreatment baseline levels after discontinuation of rhIL-12. CD56 bright NK cells expanded dramatically in the blood of a patient with baseline lymphopenia before rhIL-12 therapy. In vitro proliferation of patient PBMCs in response to IL-12 was indistinguishable from that of PBMCs obtained from healthy control subjects. Moreover, spontaneous in vitro proliferation of patient PBMCs increased significantly during rhIL-12 therapy. Increased levels of IFN-␥ and IL-18 were detected in the serum of patients treated in the 100 and 250 ng/kg dose cohorts during the first multiple dose cycle.

Coexpression of IL-18 Strongly Attenuates IL-12-Induced Systemic Toxicity through a Rapid Induction of IL-10 without Affecting its Antitumor Capacity

“…The therapeutic effects of IL-12 have been extensively demonstrated in a variety of animal tumor models when it is administrated either systemically or locally at the tumor site (4–7). Moreover, the pleiotropic antitumoral characteristics of IL-12 have encouraged the initiation of several clinical trials in patients with different types of cancer like T cell lymphoma (6), non-Hodgkin lymphoma (8, 9), melanoma (10), ovarian cancer (11), Kaposi's sarcoma (12), renal carcinoma (13), and so on.…”

Phase II study of interleukin-12 for treatment of plateau phase multiple myeloma (E1A96): A trial of the Eastern Cooperative Oncology Group

“…Studies have shown that IL-12 given in conjunction with rituximab for low-grade non-Hodgkin lymphoma is well tolerated and may be associated with longer response duration than previous trials using rituximab alone [11,12]. IL-12 has also been studied after autologous stem cell transplant for hematological malignancies resulting in the expansion of T, B, and NK cells in vivo [13]. Interleukin-12 alone or with GM-CSF has been used to enhance anti-idiotype vaccines in patients with multiple myeloma [14].…”

Gene-modified bone marrow cell therapy for prostate cancer

“…52,53 Recent reports of combination Gene-modified BMC therapy H Wang and TC Thompson therapy with immune cytokines and BM transplantation appear to provide specific advantages and a new direction for cancer therapy. 54,55 Mesenchymal stem cell vehicles. The adherent fraction of BMCs contains differentiated mesenchymal BM stromal cells and pluripotent mesenchymal stem cells (MSCs) that give rise to differentiated cells that belong to the osteogenic, chondrogenic, adipogenic, myogenic and fibroblastic lineages.…”