Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

Abstract

<p>Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.</p><p>In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3<sup>rd</sup>, 6<sup>th</sup>, 9<sup>th</sup>, and 12<sup>th</sup> months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.</p>