Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients

• Published in: Cancer Immunology, Immunotherapy Vol. 69; no. 3; pp. 383 - 397
• Main Authors: Battaglia, Alessandra, Buzzonetti, Alexia, Fossati, Marco, Scambia, Giovanni, Fattorossi, Andrea, Madiyalakan, Madi R., Mahnke, Yolanda D., Nicodemus, Christopher
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2020; Springer Nature B.V
• Subjects: Antibodies, Monoclonal, Murine-Derived - pharmacology; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Antigens; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer Research; Carboplatin; Carboplatin - pharmacology; Carboplatin - therapeutic use; CD8 antigen; Combination therapy; Female; Humans; Immune system; Immunology; Immunotherapy; Immunotherapy - methods; Lymphocytes T; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Monocytes; Oncology; Original; Original Article; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Paclitaxel; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Peripheral blood; Precision Medicine; Suppressor cells; Oregovomab; Immune response; Personalized medicine; Predictive biomarkers; Ovarian cancer
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-019-02456-z

The standard-of-care (SOC) first-line therapy for ovarian cancer (OC) patients is plagued with high relapse rates. Several studies indicated the immune system’s prominent role changing the disease course in OC patients. Chemo-immunotherapy regimens, currently being explored, include oregovomab, which is a monoclonal antibody specific for the OC associated antigen carbohydrate/cancer antigen 125 (CA125) that yielded promising results when administered together with SOC in a previous study. The QPT-ORE-002 multi-site phase II randomized study demonstrated that in patients with advanced OC, oregovomab combined with first-line SOC improved overall and progression-free survival, compared to SOC alone. The study included an Italian cohort in which we demonstrated that adding oregovomab to SOC resulted in increased patient numbers with amplified CA125-specific CD8 + T lymphocytes/ml peripheral blood counts, which might explain the improved therapeutic effect of SOC + oregovomab over SOC alone. Predictive for oregovomab efficacy was a less suppressive immune environment at baseline as indicated by low numbers of circulating myeloid-derived suppressor cells, subset type 4, and a low neutrophil-and-monocyte to lymphocyte ratio.