Biotherapy Institute of Japan

Tokyo, Japan

Biotherapy Institute of Japan

Tokyo, Japan

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Nieda M.,Biotherapy Institute of Japan | Terunuma H.,Biotherapy Institute of Japan | Terunuma H.,Southern Tohoku General Hospital | Eiraku Y.,Biotherapy Institute of Japan | And 2 more authors.
Experimental Dermatology | Year: 2015

Dendritic cells (DCs) can be differentiated from CD14+ monocytes in the presence of interferon-α (IFNα) and granulocyte/macrophage-colony stimulating factor (GM-CSF) in vitro and are known as IFN-DCs. Circulating blood CD56+ cells expressing high levels of CD14, HLA-DR and CD86 have been shown to spontaneously differentiate into DC-like cells in vitro after their isolation from blood. We show here that IFN-DCs expressing high levels of CD56 (hereafter, CD56high+ IFN-DCs) can be differentiated in vitro from monocytes obtained as adherent cells from healthy donors and patients with metastatic melanoma. These cells expressed high levels of CD14, HLA-DR and CD86 and possessed many pseudopodia. These CD56high+ IFN-DCs may be an in vitro counterpart of the circulating CD56+ CD14+ CD86+ HLA-DR+ cells in blood. Conventional mature DCs differentiated from monocytes as adherent cells in the presence of GM-CSF, IL-4 and TNF-α (hereafter, mIL-4DCs) did not express CD56 or CD14. In contrast to mIL-4DCs, the CD56high+ IFN-DCs exhibited a stronger capacity to stimulate autologous CD56+ Vγ9γδT cells highly producing IFNγ in the presence of zoledronate and IL-2. The CD56high+ IFN-DCs possessing HLA-A*0201 effectively induced Mart-1-modified melanoma peptide (A27L)-specific CD8+ T cells through preferential expansion of CD56+ Vγ9γδT cells in the presence of A27L, zoledronate and IL-2. Vaccination with CD56high+ IFN-DCs copulsed with tumor antigens and zoledronate may orchestrate the induction of various CD56+ immune cells possessing high effector functions, resulting in strong immunological responses against tumor cells. This study may be relevant to the design of future clinical trials of CD56high+ IFN-DCs-based immunotherapies for patients with melanoma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Sakurai D.,Tokyo Medical and Dental University | Iwatani Y.,National Hospital Organization Nagoya Medical Center | Ohtani H.,Tokyo Medical and Dental University | Naruse T.K.,Tokyo Medical and Dental University | And 3 more authors.
Immunogenetics | Year: 2015

Human APOBEC3H (A3H) is a member of APOBEC3 cytidine deaminase family that potently restricts HIV-1 replication. Because A3H is genetically divergent with different intracellular stability and anti-HIV-1 activity in vitro, we investigated a possible association of A3H with susceptibility to HIV-1 infection and disease progression in Japanese populations. A total of 191 HIV-1-infected individuals (HIV group), 93 long-term non-progressors to AIDS (LTNP group) and 421 healthy controls were genotyped for two functional APOBEC3H polymorphisms, rs139292 and rs139297. As compared with the controls, minor allele frequency (MAF) for rs139292 was high in the HIV group (MAF in cases vs. controls; 0.322 vs. 0.263, odds ratio (OR) = 1.33, 95 % confidence interval (95 % CI) = 1.02–1.74, p = 0.035) and low in the LTNP group (0.161 vs. 0.263, OR = 0.54, 95 % CI = 0.36–0.82, p = 0.004, pc = 0.007), whereas the MAF for rs139297 was high in the HIV group (0.367 vs. 0.298, OR = 1.36, 95 % CI = 1.07–1.76, p = 0.017, pc = 0.035). In addition, haplotype analyses revealed that the frequencies of A3H-hapC and -hapA were high (0.322 vs. 0.262, OR = 1.33, 95% CI = 1.02–1.74, p = 0.003) and low (0.634 vs. 0.697, OR = 0.75, 95 % CI = 0.58–0.97, p = 0.002), respectively, in the HIV group, whereas the frequencies of A3H-hapC and -hapB were low (0.161 vs. 0.262, OR = 0.54, 95 % CI = 0.36–0.82, p = 0.00003) and high (0.097 vs. 0.040, OR = 2.55, 95 % CI = 1.40–4.62, p = 0.000008), respectively, in the LTNP group, as compared with those in the controls. These observations suggest that the A3H with low anti-HIV-1 activity, A3H-hapC, is associated with the susceptibility to HIV-1 infection, whereas the A3H producing a stable protein, A3H-hapB, may confer a low risk of disease progression to AIDS. © 2015, Springer-Verlag Berlin Heidelberg.


Nakayama E.E.,Osaka University | Nakajima T.,Tokyo Medical and Dental University | Kaur G.,All India Institute of Medical Sciences | Mimaya J.-I.,Shizuoka Childrens Hospital | And 4 more authors.
AIDS Research and Human Retroviruses | Year: 2013

TRIM5α is a factor contributing to intracellular defense mechanisms against retrovirus infection. Rhesus and cynomolgus monkey TRIM5αs potently restrict HIV-1, whereas human TRIM5α shows weak effects against HIV-1. We investigated the association between a single nucleotide polymorphism in the TRIM5α linker 2 region (rs11038628), which substituted aspartic acid (D) for glycine (G) at position 249, with susceptibility to HIV-1 infection in Japanese and Indian subjects. rs11038628 is rare in Europeans but common in Asians and Africans. Functional analyses were performed by multiple-round replication and single-round assays, and indicated that the G249D substitution attenuated anti-HIV-1 activity of human TRIM5α. A slight attenuation of anti-HIV-2 activity was also observed in TRIM5α with 249D. The predicted secondary structure of the linker region suggested that the 249D substitution extended the α-helix in the neighboring coiled-coil domain, suggesting that human TRIM5α with 249D may lose the flexibility required for optimal recognition of retroviral capsid protein. We further analyzed the frequency of G249D in Japanese (93 HIV-1-infected subjects and 279 controls) and Indians (227 HIV-1-infected subjects and 280 controls). The frequency of 249D was significantly higher among HIV-1-infected Indian subjects than in ethnicity-matched control subjects [odds ratio (OR)=1.52, p=0.026]. A similar weak tendency was observed in Japanese subjects, but it was not statistically significant (OR=1.19, p=0.302). In conclusion, G249D, a common variant of human TRIM5α in Asians and Africans, is associated with increased susceptibility to HIV-1 infection. © Mary Ann Liebert, Inc.


Patent
Biotherapy Institute Of Japan | Date: 2014-10-07

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD3 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.


Patent
Biotherapy Institute Of Japan | Date: 2012-12-19

It is intended to provide a method for producing an NK cell-enriched blood product, the method being less invasive and capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, a bisphosphonate derivative or a salt thereof, or a hydrate thereof, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood product.


Patent
Biotherapy Institute Of Japan | Date: 2013-03-27

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD137 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.


Patent
Biotherapy Institute Of Japan | Date: 2012-01-17

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD3 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.


Patent
Biotherapy Institute Of Japan | Date: 2013-11-27

It is intended to provide a method for producing an NK cell-enriched blood preparation, which is low invasive and is capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, an anti-CD3 antibody, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood preparation.


Trademark
Biotherapy Institute Of Japan | Date: 2012-06-05

Biological tissue cultures other than for medical and veterinary purposes. Biological tissue cultures for medical purposes. Incubators for bacteria culture; Laboratory equipment and supplies, namely, incubators; Cell culture kits for normal human Blood vascular endothelial cell; Cell culture kits for natural killer cell.


Patent
Biotherapy Institute Of Japan | Date: 2011-02-04

It is intended to provide a method for producing an NK cell-enriched blood product, the method being less invasive and capable of conveniently and rapidly growing NK cells, etc. in blood collected from an organism. The NK cells in blood are stimulated with NK cell growth-stimulating factors comprising an anti-CD16 antibody, OK432, a bisphosphonate derivative or a salt thereof, or a hydrate thereof, and a cytokine. Then, the blood is cultured at a physiological cell temperature to produce an NK cell-enriched blood product.

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