Title
In vivo anti-V-ATPase antibody treatment delays ovarian tumor growth by increasing antitumor immune responses
Recommended Citation
Kulshrestha A, Katara GK, Ibrahim SA, Riehl VE, Schneiderman S, Bilal M, Young AN, Levine S, Fleetwood S, Dolan J, Gilman-Sachs A, Beaman KD. In vivo anti-V-ATPase antibody treatment delays ovarian tumor growth by increasing antitumor immune responses. Mol Oncol. 2020 Oct;14(10):2436-2454. doi: 10.1002/1878-0261.12782. Epub 2020 Sep 10. PMID: 32797726; PMCID: PMC7530789
Abstract
Tumor acidity is the key metabolic feature promoting cancer progression and is modulated by pH regulators on a cancer cell's surface that pump out excess protons/lactic acid for cancer cell survival. Neutralizing tumor acidity improves the therapeutic efficacy of current treatments including immunotherapies. Vacuolar-ATPase (V-ATPase) proton pumps encompass unique plasma membrane-associated subunit isoforms, making this molecule an important target for anticancer therapy. Here, we examined the in vivo therapeutic efficacy of an antibody (a2v-mAB) targeting specific V-ATPase-'V0a2' surface isoform in controlling ovarian tumor growth. In vitro a2v-mAb treatment inhibited the proton pump activity in ovarian cancer (OVCA) cells. In vivo intraperitoneal a2v-mAb treatment drastically delayed ovarian tumor growth with no measurable in vivo toxicity in a transplant tumor model. To explore the possible mechanism causing delayed tumor growth, histochemical analysis of the a2v-mAb-treated tumor tissues displayed high immune cell infiltration (M1-macrophages, neutrophils, CD103
Document Type
Article
PubMed ID
32797726
DOI
10.1002/1878-0261.12782
Affiliations
Department of Obstetrics & Gynecology, Advocate Lutheran General Hospital