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Extracellular vesicles (EVs) are considered as important mediators of intercellular communication, which carry a diverse repertoire of genetic information between cells. This feature of EVs can be used and improved to advance their therapeutic potential. We have previously shown that genetically engineered EVs carrying the suicide gene mRNA and protein—cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT)—inhibited schwannoma tumor growth in vivo. To further examine whether this approach can be applied to other cancer types, we established a subcutaneous xenograft glioblastoma tumor model in mice, as glioblastoma represents the most common primary brain tumor, which is highly aggressive compared with the original schwannoma tumor model. U87-MG glioblastoma cells were implanted into the flanks of nude SCID mice, and the animals were intratumorally injected with the EVs isolated from the cells expressing EGFP or CD-UPRT. After the intraperitoneal administration of the prodrug 5-fluorocytosine, the tumor growth was assessed by regular caliper measurements. Our data revealed that the treatment with the CD-UPRT-enriched EVs significantly reduced the tumor growth in mice. Taken together, our findings suggest that EVs uploaded with therapeutic CD-UPRT mRNA/protein may be a useful tool for glioblastoma treatment.

We employed antibody pre-conditioning with alemtuzumab and posttransplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients between January 2004 and December 2005. Mean recipient age was 10.7 ± 5.8 years, 7.7 were undergoing retransplantation, and 3.8 were sensitized, with a PRA >20. Mean donor age was 32.8 ± 9.2 years. Living donors were utilized in 65 of the transplants. Mean cold ischemia time was 27.6 ± 6.4 h. The mean number of HLA mismatches was 3.3 ± 1.3. Mean follow-up was 25 ± 8 months. One and 2 year patient survival was 100 and 96. One and 2 year graft survival was 96 and 88. Mean serum creatinine was 1.1 ± 0.6 mgdL, and calculated creatinine clearance was 82.3 ± 29.4 mLmin1.73 m2. The incidence of pre-weaning acute rejection was 11.5; the incidence of delayed graft function was 7.7. Eighteen (69) of the children were tapered to spaced tacrolimus monotherapy, 10.5 ± 2.2 months after transplantation. The incidence of CMV, PTLD and BK virus was 0; the incidence of posttransplant diabetes was 7.7. Although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation.

We employed antibody pre-conditioning with alemtuzumab and posttransplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients between January 2004 and December 2005. Mean recipient age was 10.7 ± 5.8 years, 7.7% were undergoing retransplantation, and 3.8% were sensitized, with a PRA >20%. Mean donor age was 32.8 ± 9.2 years. Living donors were utilized in 65% of the transplants. Mean cold ischemia time was 27.6 ± 6.4 h. The mean number of HLA mismatches was 3.3 ± 1.3. Mean follow-up was 25 ± 8 months. One and 2 year patient survival was 100% and 96%. One and 2 year graft survival was 96% and 88%. Mean serum creatinine was 1.1 ± 0.6 mg/dL, and calculated creatinine clearance was 82.3 ± 29.4 mL/min/1.73 m2. The incidence of pre-weaning acute rejection was 11.5%; the incidence of delayed graft function was 7.7%. Eighteen (69%) of the children were tapered to spaced tacrolimus monotherapy, 10.5 ± 2.2 months after transplantation. The incidence of CMV, PTLD and BK virus was 0%; the incidence of posttransplant diabetes was 7.7%. Although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation.