花園 豊

サルにヒト蛋白質を投与すると免疫学的に排除されることがある.本研究ではまず2頭のカニクイザルにヒトエリスロポエチン(hEPO)を投与すると抗hEPO抗体が産生される事を示した.次に2頭のサルを用いてシクロスポリン(CyA)併用投与を行ったところ副作用無く抗体は検出されずhEPOの十分な血中濃度が得られヘモグロビン濃度の上昇を認めた.CyA投与はヒト蛋白質投与に伴う免疫反応の予防に有用である

Adenoviral vectors primarily derived from the adenovirus serotype 5 (Ad5) are widely used for many gene transfer applications. However, they cannot efficiently infect hematopoietic cells because these cells barely express the coxsakie-adenoviral receptor (CAR). In this study, we developed a soluble fusion protein linking viral fibers and the c-Kit receptor to alter Ad5 tropism to immature hematopoietic cells. The CAR-SCF fusion protein consists of two extracellular domains of human CAR and mouse stem cell factor (SCF). CAR-SCF was added to culture of various human hematopoietic cell lines together with an Ad vector expressing the eGFP gene driven by the CMV promoter. CAR-SCF greatly enhanced Ad5-mediated gene transfer and eGFP expression in c-Kit<SUP>+</SUP> cell lines. The ability of CAR-SCF to enhance Ad5 vector infectivity was dependent on cellular c-Kit expression levels. Furthermore, CAR-SCF also enhanced Ad5 vector transfection into human cord blood CD34<SUP>+</SUP> cells. In conclusion, the fusion protein will allow us to efficiently retarget adenoviral vectors to c-Kit<SUP>+</SUP> human immature hematopoietic cells by just adding the fusion protein to transduction culture with adenoviral vectors. This method has an advantage that all conventional Ad5 vectors can be used to infect hematopoietic cells without any reconstruction or modification of the vectors.

Here we report a 65-year-old male patient with idiopathic myelofibrosis (IMF) accompanied with acromegaly. He was admitted because of anemia and splenomegaly. No favorable effects were observed when hydroyurea was administered. However, his symptoms were successfully treated by administration of vincristine and prednisolone (VP therapy), which is usually applied for choronic myelogenous leukemia in the accelerated phase. Therefore, VP therapy might be one possible for IMF. Since there have been several reports suggesting the possible association of hematological malignancies with acromegaly, we speculate that acromegaly was implicated in the initiation or progression of IMF in this case.