Racotumomab and PD-1 blockade combination exhibits an additive antitumor effect in a non-small cell lung cancer model

VALERIA I. SEGATORI; CYNTHIA A. GULINO; CARLA S. CAPOBIANCO; SELENE ROJO; GRETEL M. FERREIRA; HECTOR A. CUELLO; MARIANO R. GABRI; DANIEL F. ALONSO

Congreso; AACR Virtual Annual Meeting; 2020

American Association for Cancer Research (AACR)

N-glycolylneuraminic acid (NeuGc) is a sialic acid molecule present in mammaliancells as terminal constituent of membrane glycoconjugates such as gangliosides andglycoproteins. Although the role of NeuGc-containing glycoconjugates in humancancer is still under investigation, gangliosides such as NeuGcGM3 has beenconsistently reported as a tumor antigen in various epithelial and neuroectodermalmalignancies, including non-small cell lung cancer (NSCLC). Interestingly, NeuGcglycoconjugates are abundant in aggressive neoplasms, but they are usually absentin normal human tissues. In contrasts to most mammals, human beings lack the keyenzyme that catalyzes N-glycolylation of sialic acid. Cancer cells can favor NeuGcintake from diet sources, thus allowing the expression of NeuGc-containingglycoconjugates. Racotumomab is an anti-NeuGc anti-idiotype monoclonal antibodythat has been approved in Latin American countries as maintenanceimmunotherapy for advanced NSCLC. Combinatorial approaches involving long-termimmunization against tumor-specific antigens together with the anti-PD1 immunecheckpoint inhibitor pembrolizumab is an attractive strategy for immunotherapy. Inthis work, we have examined the antitumor activity of racotumomab in combinationwith anti-PD1 therapy, using the 3LL Lewis lung carcinoma as a preclinical model ofNSCLC in C57BL/6 mice. Immunization with either weekly or biweekly sc doses ofracotumomab at 50-200 μg/dose formulated in aluminum hydroxide(racotumomab-alum) demonstrated a significant antitumor effect against theprogression of lung tumor nodules (p