Antitumor effect of large doses IL-2-activated HLA haploidentical peripheral blood stem cells on refractory metastatic solid tumor treatment

Objectives: The traditional inununotherapy for patients with refractory metastatic solid tuniors is limited because tionors induce inununosuppression. New treatment is, therefore, needed. The aim of this studv was to evaluate the clinical efficacy of infusion of high-dose interleukin (IL)-2 -activated allogeneic haploidentical peripheral blood stem cells (haplo-PBSCTs) on patients with an advanced stage of refractory solid tionors. Methods: This study involved 11 patients with refractory metastatic tumors and haploidentical relatives as donors for haplo-PBSCs. The therapeutic outcome of the IL-2activated haplo-PBSC infusion and patients ' cytokine levels were evaluated. The cytotoxicity of IL2-activated haplo-PBSCs, for tinnor cells was determined using in vitro cytotoxicity assays. Results: A range from 2.5 to 5.6 X 10(10) of activated haplo-PBSCs were harvested after exposure to rhIL-2, along with a significant increase in the proportion of natural killer (NK) cells and activated lyinphocvtes (CD69(+) and CD25(+)), and enhanced cytotoxicity of haplo-PBSCs for several tunlor cell lines. FollowIng treatment, 1 (1/11) patient achieved a partial response (PR), 1 (1/11) achieved a nzild response (MR), 6 (6/11) achieved stable disease (SD), and 3 (3/11) achieved progressive disease (PD). For all of the I I patients, the median progression-free survival (PFS) was 5 inonths (3-14 months). We also observed the phenomenon of Th2 shifted to Th1, which played a crucial role in cancer inununotherapy. Conclusions: The adoptive transfusion of IL-2-activated haplo-PBSCs has potent antitumor effects both in vitro and in vivo. Thisfinding suggests that IL-2-activated haploPBSCs maY serve as an alternative therapy for advanced-stage solid tumors, especially,for those patients who are refractory or ineligible,for cheino- or radiotherapy.