IRX‐2 and Thymosin α1 (Zadaxin) Increase T Lymphocytes in T Lymphocytopenic Mice and Humans

Abstract

Mouse studies showed a synergy of thymosin alpha1 (Talpha1) and a natural cytokine mixture (IRX-2) in increasing T lymphocyte number and responses. Clinical studies with IRX-2 showed increases of T lymphocytes in lymphocytopenic cancer patients but relatively little effect on irradiated, lymphocytopenic patients. The present phase 1 and 2 study shows that Talpha1 enhances the effect of IRX-2 in these lymphocytopenic patients. Patients (seven) were treated with subcutaneously injected IRX-2 (200 units IL-2 equivalence), Talpha1 (1.6 mg/day) (four patients), or the combination of IRX-2 and Talpha1 (seven patients) daily for 10 days. Peripheral blood lymphocytes (T, B, NK) and subsets (CD4, CD8) were measured at the start of treatment and on day 11. IRX-2 and Talpha1 had little or no significant effect. The combination markedly increased various lymphocyte populations (>350 cells/microL). Four patients followed for 6 weeks displayed sustained increases involving both naïve and memory T cells. Responses to persistent infections were observed in three of the four patients and no significant toxicity was observed. Talpha1 and IRX-2 synergize to increase safely T cells in lymphocytopenic patients.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

“…Moreover, IL-15, IL-2, IFN-α, and IL-21 (22) have been demonstrated to promote NK- and CD8 + T cell-mediated cytotoxicity, to sustain function, and to increase antitumor immunity. Animal studies have shown that Tα1 had no effect on T cell numbers (both CD4 + and CD8 + ), and therefore, had no effect on T lymphocyte proliferation (23). Therefore, our in vitro data are consistent with this finding.…”

IRX-2, a novel biologic, favors the expansion of T effector over T regulatory cells in a human tumor microenvironment model

“…The delivery of IRX-2 to tumor-draining lymph nodes (LN) of HNC patients reduced pain and dysphagia, decreased tumor size and, in some patients, prolonged disease-free and overall survival [1, 2]. IRX-2 also increased the number of circulating naive and memory T cells [3], enriched T cells in tumor-draining LN [4], and promoted lymphocyte infiltrations into the tumors [5]. In addition, in vitro studies showed that IRX-2 enhanced dendritic cell (DC) maturation [6] and protected cytotoxic T lymphocytes from tumor-induced apoptosis [7].…”

Head and neck cancer immunotherapy: Clinical evaluation

“…Similarly, Hadden et al [25] have reported promising histological outcomes in SCCHN patients immunized with IRX-2, a natural cytokine mixture of IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-, granulocyte colony-stimulating factor, GM-CSF, and IFN-from activated peripheral blood mononuclear cells. Compared with controls, patients with advanced SCCHN who received a 21-day course of this immunostimulant showed evidence of dendritic cell maturation, a qualitative difference in lymph node architecture and size, as well as increased intranodal T/B cell infiltration.…”

“…Compared with controls, patients with advanced SCCHN who received a 21-day course of this immunostimulant showed evidence of dendritic cell maturation, a qualitative difference in lymph node architecture and size, as well as increased intranodal T/B cell infiltration. They also showed significant increases in numbers of tumor-infiltrating lymphocytes [25]. A phase 3 trial is being planned.…”