Antitumor effect of large doses IL-2-activated HLA haploidentical peripheral blood stem cells on refractory metastatic solid tumor treatment.
OBJECTIVE
The traditional immunotherapy for patients with refractory metastatic solid tumors is limited because tumors induce immunosuppression. New treatment is, therefore, needed. The aim of this study 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 tumors.


METHODS
This study involved 11 patients with refractory metastatic tumors and haploidentical relatives as donors for haplo-PBSCs. The therapeutic outcome of the IL-2-activated haplo-PBSC infusion and patients' cytokine levels were evaluated. The cytotoxicity of IL-2-activated haplo-PBSCs for tumor 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 lymphocytes (CD69+ and CD25+), and enhanced cytotoxicity of haplo-PBSCs for several tumor cell lines. Following treatment, 1 (1/11) patient achieved a partial response (PR), 1 (1/11) achieved a mild response (MR), 6 (6/11) achieved stable disease (SD), and 3 (3/11) achieved progressive disease (PD). For all of the 11 patients, the median progression-free survival (PFS) was 5 months (3-14 months). We also observed the phenomenon of Th2 shifted to Th1, which played a crucial role in cancer immunotherapy.


CONCLUSIONS
The adoptive transfusion of IL-2-activated haplo-PBSCs has potent antitumor effects both in vitro and in vivo. This finding suggests that IL-2-activated haplo-PBSCs may serve as an alternative therapy for advanced-stage solid tumors, especially for those patients who are refractory or ineligible for chemo- or radiotherapy.
Ren
Xiu-Bao
XB
Department of Immunology & Biotherapy, Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tianjin, People's Republic of China, China.
Yu
Jin-Pu
JP
Cao
Shui
S
Ren
Bao-Zhu
BZ
Li
Hui
H
Liu
Hong
H
Min
Wei-Ping
WP
Hao
Xi-Shan
XS
D000328:Adult; D000368:Aged; D001782:Blood Donors; D002454:Cell Differentiation; D005260:Female; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D010641:Phenotype; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D006680:HLA Antigens; D007376:Interleukin-2