TY - JOUR
T1 - Anti-GD2 immunoliposomes loaded with oxamate for neuroblastoma
AU - Panosyan, William S.
AU - Panosyan, Daniel E.
AU - Koster, Jan
AU - Panosyan, Eduard H.
N1 - Funding Information: Manuscript review and constructive criticism by Dr Araz Marachelian (Children’s Hospital Los Angeles), and Dr Clarke Anderson (City of Hope, Duarte, California) are highly appreciated. Publisher Copyright: © 2023, The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
PY - 2023/8
Y1 - 2023/8
N2 - Abstract: Oncometabolism can be targeted for the development of less myelotoxic oncotherapeutics. Lactate dehydrogenase A (LDHA) is central to the Warburg effect, a potential oncometabolic shift in neuroblastoma (NBL). Advanced surgical, cytotoxic and cell-differentiating therapies improved survival of children with NBL. Anti-GD2 monoclonal antibodies (mAb) effectively targeting NBL are also incorporated into complex therapies. However, poor clinical outcomes of high-risk NBL require improvements. Here, we verified the pre-reported prognostic value of LDHA expression in NBL using the R2 onco-genomics platform. Kaplan–Meier curves re-demonstrated that higher tumor LDHA expression correlates with worse survival. Multivariate statistics confirmed LDHA is independent from age, stage, and MYCN amplification. In conclusion, a molecular construct is proposed with anti-GD2 mAbs utilized for the targeted delivery of liposomes containing an LDHA inhibitor, Oxamate. Development and preclinical testing of this immunoliposome may validate targeted inhibition of the Warburg effect for NBL. Impact: Development of therapeutics against oncometabolism.Targeted specified drug-delivery with mAb.Sparing normal tissues from profound LDHA inhibition.Immunoliposome loaded with an anti-metabolite.If preclinically successful, has translational potential.
AB - Abstract: Oncometabolism can be targeted for the development of less myelotoxic oncotherapeutics. Lactate dehydrogenase A (LDHA) is central to the Warburg effect, a potential oncometabolic shift in neuroblastoma (NBL). Advanced surgical, cytotoxic and cell-differentiating therapies improved survival of children with NBL. Anti-GD2 monoclonal antibodies (mAb) effectively targeting NBL are also incorporated into complex therapies. However, poor clinical outcomes of high-risk NBL require improvements. Here, we verified the pre-reported prognostic value of LDHA expression in NBL using the R2 onco-genomics platform. Kaplan–Meier curves re-demonstrated that higher tumor LDHA expression correlates with worse survival. Multivariate statistics confirmed LDHA is independent from age, stage, and MYCN amplification. In conclusion, a molecular construct is proposed with anti-GD2 mAbs utilized for the targeted delivery of liposomes containing an LDHA inhibitor, Oxamate. Development and preclinical testing of this immunoliposome may validate targeted inhibition of the Warburg effect for NBL. Impact: Development of therapeutics against oncometabolism.Targeted specified drug-delivery with mAb.Sparing normal tissues from profound LDHA inhibition.Immunoliposome loaded with an anti-metabolite.If preclinically successful, has translational potential.
UR - http://www.scopus.com/inward/record.url?scp=85148013720&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41390-023-02479-4
DO - https://doi.org/10.1038/s41390-023-02479-4
M3 - Article
C2 - 36788290
SN - 0031-3998
VL - 94
SP - 458
EP - 461
JO - Pediatric Research
JF - Pediatric Research
IS - 2
ER -