1. IntroductionRacotumomab [1] is a monoclonal antibody (Mab) of murineanti-idiotype (Ab2) generated by immunizing BALB/c mice withthe P3 monoclonal antibody [2], a Mab (Ab1) that specificallyrecognizes N-glycolylated gangliosides, sulfated glycolipids, andantigens present in various types of human tumors includingthose located in lung [3–7]. We hypothesize that RacotumomabMab contains a structural mimicry of ganglioside N-glycolyl GM3(NeuGc-GM3). The vaccine formulation of Racotumomab/aluminais capable of inducing antitumor effects in murine models [7].Among the observed antitumor effects in the murine model accounta decrease in metastases, increased apoptosis of metastatic cells∗Corresponding author. Tel.: +537 214 3174.E-mail address: katiar@cim.sld.cu (K. de la Luz-Hernández).and a marked decrease in angiogenesis as well as higher amount ofCD4 T-lymphocytes and T-tumor infiltrating CD8 [13]. The safetyand immunogenicity of vaccination with idiotypic Racotumomabhas been shown in clinical phase I trials in patients with breastcancer and melanoma [4,8]. In these vaccinated patients a hightiter of antibodies specific to NeuGc-GM3 was detected and anantibody response against NeuGc-GM3 was also found which isnot suppressed by the absorption of the serum with RacotumomabMab suggesting that immunization with Racotumomab idiotypeprobably induces natural immune response against tumors [4,8].Phase I clinical trials in NSCLC patients have also been conductedwith encouraging clinical results [9]. For phase I and II clinical tri-als, mAb-Racotumomab was produced in mice ascites, a commonpractice in the 1990s for small scale antibody production.We developed a new bioreactor-based process usingprotein-free media for the production of mAb-Racotumomab.Given the increase in production volume, it was necessary to
1. IntroductionRacotumomab [1] is a monoclonal antibody (Mab) of murineanti-idiotype (Ab2) generated by immunizing BALB/c mice withthe P3 monoclonal antibody [2], a Mab (Ab1) that specificallyrecognizes N-glycolylated gangliosides, sulfated glycolipids, andantigens present in various types of human tumors includingthose located in lung [3–7]. We hypothesize that RacotumomabMab contains a structural mimicry of ganglioside N-glycolyl GM3(NeuGc-GM3). The vaccine formulation of Racotumomab/aluminais capable of inducing antitumor effects in murine models [7].Among the observed antitumor effects in the murine model accounta decrease in metastases, increased apoptosis of metastatic cells∗Corresponding author. Tel.: +537 214 3174.E-mail address: katiar@cim.sld.cu (K. de la Luz-Hernández).and a marked decrease in angiogenesis as well as higher amount ofCD4 T-lymphocytes and T-tumor infiltrating CD8 [13]. The safetyand immunogenicity of vaccination with idiotypic Racotumomabhas been shown in clinical phase I trials in patients with breastcancer and melanoma [4,8]. In these vaccinated patients a hightiter of antibodies specific to NeuGc-GM3 was detected and anantibody response against NeuGc-GM3 was also found which isnot suppressed by the absorption of the serum with RacotumomabMab suggesting that immunization with Racotumomab idiotypeprobably induces natural immune response against tumors [4,8].Phase I clinical trials in NSCLC patients have also been conductedwith encouraging clinical results [9]. For phase I and II clinical tri-als, mAb-Racotumomab was produced in mice ascites, a commonpractice in the 1990s for small scale antibody production.We developed a new bioreactor-based process usingprotein-free media for the production of mAb-Racotumomab.Given the increase in production volume, it was necessary to
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