Racotumomab antitumor activity in the murine model of non small cell lung carcinoma 3LL is related with the level of expression on NGcGM3

SEGATORI VI; GOMEZ DE; ALONSO DF; GABRI MR

Congreso; 103rd Annual Meeting of the American Association for Cancer Research; 2012

N-Glycolylneuraminic acid (NGc) is a sialic acid molecule found in most mammalian cells. It is usually found as terminal constituents of different membrane glycoconjugates such as the GM3 ganglioside (NGcGM3) and has been described as tumor antigen in non small cell lung cancer (NSCLC) in humans. However, most mouse cancer cell lines, such as 3LL NSCLC, are negative for the expression of this antigen although mice somatic cells frequently express it. It was reported that minor component of the ganglioside fraction derived from primary tumors of 3LL is NGcGM3. Interestingly in metastatic lesions the presence of NGcGM3 reach the 73.4% of total lipid bound sialic acid. Anti idiotypic antibodies (Ab2) are proposed as therapeutic vaccines when they bear the internal image of tumor antigens. Racotumomab is a gamma type anti idiotypic antibody that is able to trigger a strong anti anti idiotypic antibody (Ab3) response. These Ab3 antibodies have the same antigenic specificity than the Ab1 (P3) but they are substantially different from the internal image of it. Additionally, since it was demonstrated that immunization with Racotumomab elicited an anti NGcGM3 antibody response in humans, the question about to what extent the presence of the vaccine target antigen in the tumor decides the effect of the active treatment remains open. In this work, we evaluated the association of NGcGM3 expression in tumor cells in relation to the antitumor activity of the vaccine. Evaluation of Racotumomab antitumor activity over 3LL primary tumor showed no difference in tumor growth rate between treated and control mice. Moreover, the vaccine showed no antitumor activity in the metastatic dissemination in C57BL/6 mice treated with iv 3LL cells. However, when Racotumomab activity was evaluated in a spontaneous metastasis model it was observed a reduction in lung metastatic nodules in treated group compared to the control. The amount of NGcGM3 in 3LL cells can be increased by preincubation in vitro with purified NGc. Using this NGcGM3 positive metastasis model, we observed that Racotumomab was able to develop an active antitumor activity. The number of experimental metastases was reduced significantly between control and treated group (3.5 (1-18) vs 0.5(1-10), control vs Racotumomab. p