PMID- 28504465
OWN - NLM
STAT- MEDLINE
DCOM- 20180529
LR  - 20180529
IS  - 2472-1727 (Electronic)
VI  - 109
IP  - 11
DP  - 2017 Jul 3
TI  - Effects of SA237, a humanized anti-interleukin-6 receptor monoclonal antibody, on 
      pre- and postnatal development in cynomolgus monkey.
PG  - 843-856
LID - 10.1002/bdr2.1036 [doi]
AB  - BACKGROUND: SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal 
      antibody in which the constant and variable regions have been engineered for a 
      longer plasma half-life. According to literature, blocking of IL-6 related 
      functions could have an influence on pregnancy sustainment, development of the 
      immune system, and brain growth. METHODS: SA237 effects on dams, embryo-fetal 
      development, parturition and postnatal development were investigated in an 
      enhanced pre- and postnatal development study, in which SA237 was subcutaneously 
      administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once 
      weekly from gestation day 20 until parturition. Infant development, including 
      immune function and learning ability tests, was comprehensively assessed at 
      multiple examinations until approximately 10 months after birth. RESULTS: SA237 
      plasma concentrations were almost equivalent between dams and their infants and 
      dropped throughout the postnatal period, pharmacologically relevant exposure was 
      maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to 
      IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams 
      and infants. However, there were no SA237-related adverse effects on dams, 
      embryos, fetuses, or infants. SA237 pharmacological effects contributed to the 
      suppression of plasma cell differentiation and antibody production by inhibiting 
      IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed 
      in infants, but physiological immunoglobulin class switching and general antibody 
      production against a T cell-dependent antigen were maintained. CONCLUSION: The 
      exposure to SA237 did not adversely affect dams, embryo-fetal development, 
      parturition, and postnatal development, including immune function and neuronal 
      development. Birth Defects Research 109:843-856, 2017. (c) 2017 Wiley Periodicals, 
      Inc.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Katagiri, Ryuichi
AU  - Katagiri R
AUID- ORCID: 0000-0002-5481-4064
AD  - Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
FAU - Ishihara-Hattori, Kana
AU  - Ishihara-Hattori K
AD  - Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
FAU - Frings, Werner
AU  - Frings W
AD  - Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
FAU - Amano, Jun
AU  - Amano J
AD  - Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
FAU - Fuchs, Antje
AU  - Fuchs A
AD  - Covance Preclinical Services GmbH, Muenster, Germany.
FAU - Chiba, Shuichi
AU  - Chiba S
AD  - Research Division, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170515
PL  - United States
TA  - Birth Defects Res
JT  - Birth defects research
JID - 101701004
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-6)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies, Monoclonal/blood/pharmacology
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Antibody Formation/drug effects
MH  - Embryonic Development/drug effects
MH  - Female
MH  - Fetal Development/drug effects
MH  - Fetus/drug effects
MH  - Immune System/drug effects
MH  - Interleukin-6/pharmacology
MH  - Lactation/drug effects
MH  - Macaca fascicularis
MH  - Maternal Exposure/adverse effects
MH  - Parturition/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Receptors, Interleukin-6/*antagonists & inhibitors/*immunology
OTO - NOTNLM
OT  - IL-6
OT  - SA237
OT  - antibody
OT  - development
OT  - ePPND
OT  - infant
OT  - monkey
EDAT- 2017/05/16 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/05/16 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/03/24 00:00 [revised]
PHST- 2017/03/24 00:00 [accepted]
PHST- 2017/05/16 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/05/16 06:00 [entrez]
AID - 10.1002/bdr2.1036 [doi]
PST - ppublish
SO  - Birth Defects Res. 2017 Jul 3;109(11):843-856. doi: 10.1002/bdr2.1036. Epub 2017 
      May 15.