A robust immune system conditions the response to abagovomab (anti-idiotypic monoclonal antibody mimicking the CA125 protein) vaccination in ovarian cancer patients

Autor: Giovanni Scambia, Alexia Buzzonetti, Andrea Fattorossi, Marco Fossati, Alessandra Battaglia
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
medicine.medical_treatment
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Antibodies
Monoclonal
Murine-Derived
Enterotoxins
0302 clinical medicine
Monoclonal
Immunology and Allergy
Abagovomab
Interferon-γ
Cells
Cultured
Predictive assay
Ovarian Neoplasms
Cultured
Vaccination
Antibodies
Monoclonal
Antibodies
Anti-Idiotypic
medicine.anatomical_structure
Anti-Idiotypic
030220 oncology & carcinogenesis
Female
Immunotherapy
Immunocompetence
medicine.drug
medicine.medical_specialty
medicine.drug_class
T cell
Cells
Immunology
Antineoplastic Agents
Monoclonal antibody
Cancer Vaccines
Antibodies
03 medical and health sciences
Interferon-gamma
Immune system
Ovarian cancer
Internal medicine
medicine
Humans
Personalised treatment
CA-125 Antigen
Membrane Proteins
Neoplasm Staging
Survival Analysis
business.industry
Cancer
medicine.disease
030104 developmental biology
Settore MED/40 - GINECOLOGIA E OSTETRICIA
business
CD8
Popis: Introduction Despite encouraging phase I and II study results, vaccination of ovarian cancer patients with abagovomab – an anti-idiotypic mAb that mimics the ovarian cancer CA125 protein – failed to demonstrate efficacy in the phase III trial named MIMOSA (NCT00418574). We postulated that in this trial patients with a more robust immune system did respond to abagovomab but went undetected among a larger number of non-responders. We also postulated that assessment of the immune system status ahead of abagovomab administration might predict patients’ propensity to respond to abagovomab. Materials and methods The immune system status was assessed as percentage and absolute count of CD8+ T cells producing IFN-γ after stimulation with Staphylococcal Enterotoxin B (SEB) in 80 patients on abagovomab and 31 patients on placebo from the MIMOSA trial ahead of treatment. Optimal cutoffs of the two variables were calculated by the web application “Cutoff Finder” as the points with most significant (log-rank test) splits based on relapse-free survival (RFS). The Kaplan–Meier curves and log-rank test served to estimate and compare RFS in patients with percentage and absolute count of IFN-γ producing CD8+ T cells around the cutoffs. Results Patients on abagovomab with IFN-γ producing CD8+T cell percentage above the cutoff had a better RFS (p = 0.042) than those with IFN-γ producing CD8+T cell percentage below the cutoff. Patients on abagovomab with IFN-γ producing CD8+T cell absolute count above the cutoff had a better RFS (p = 0.019) than those with IFN-γ producing CD8+T cell absolute counts below the cutoff. Consistently, the RFS of patients on abagovomab with IFN-γ producing CD8+T cell percentage and absolute counts values below the respective cutoffs was identical to that of patients on placebo. Neither the percentage nor the absolute count of IFN-γ producing CD8+T cells correlated with RFS in patients on placebo. Conclusions A robust immune system is essential to obtain a clinical response in OC patients undergoing abagovomab immunotherapy whereas a robust immune system does not confer per se a survival advantage. Further work will clarify whether the results shown here apply only in the present setting or extend to other types of cancer and/or immunotherapeutic agents.
Databáze: OpenAIRE
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