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Introduction to Vaccination
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Nezih Pişkinpaşa, Ömer Faruk Karasakal
Anti-idiotypic vaccines include antibodies called idiotopes with three-dimensional immunogenic regions, consisting of protein sequences that bind to cell receptors. Idiotopes are collected in idiotypes specific to the target antigen. An example of an anti-idiotype antibody is racotumomab. It is prepared in the experimental animal against a specific antigen. The resulting antibodies are administered to a different experimental animal to form anti-idiotype antibodies and may be used in immunization. Thus, a protective immunity is formed (Allen and Ansel 2013; Akbuğa 2002).
CIMAvax-EGF, a therapeutic non-small cell lung cancer vaccine
Published in Expert Opinion on Biological Therapy, 2018
Marco Tagliamento, Erika Rijavec, Giulia Barletta, Federica Biello, Giovanni Rossi, Francesco Grossi, Carlo Genova
A phase I combination study of CIMAvax-EGF and Vaxira was conducted among 20 advanced stage NSCLC patients who were progressing after a first-line platinum-based chemotherapy. Vaxira is composed of racotumomab, a monoclonal Ab against specific glycolylated gangliosides (NeuGcGM3) present in tumor cells, and Al. Median OS was 6.7 months. The combination resulted safe. Only mild adverse events were reported, mainly characterized by injections site reactions. All the patients were classified as GAR. Immunogenicity of racotumomab was likewise proven. Results of efficacy trials are needed [18].
Targeting glyco-immune checkpoints for cancer therapy
Published in Expert Opinion on Biological Therapy, 2021
Direct targeting of tumor-associated glycans was also developed for several cancer types. Although this approach was not intended to directly disrupt the glyco-immune checkpoint axis, it provides evidence for the role of glycans in the tumor microenvironment. Targeting tumor-associated glycans with mAb promote antibody-dependent cellular cytotoxicity (ADCC). GD2 and GD3 gangliosides are enriched in melanoma and neuroblastoma and are associated with tumor progression and metastasis [38–41]. Indeed, dinutuximab, an anti-GD2 mAb, was approved for the treatment of high-risk neuroblastoma in pediatric patients [95]. Other antibodies targeting GD2 and GD3 are under investigation and have shown promising results in several clinical trials (i.e. NCT03860207, NCT02502786, NCT00089258, NCT00002458, NCT01757626). Another ganglioside containing the non-human sialic acid Neu5Gc, Neu5GcGM3, has been proposed as a very specific cancer biomarker. Racotumomab, an anti-idiotypic Neu5GcGM3 antibody, was shown to elicit ADCC in preclinical and clinical trials [96] and its safety and efficacy are currently under evaluation in a phase 3 clinical trial in patients with non-small cell lung cancer (NCT01460472). Several other mAbs recognizing Lewis antigens (Le), such as BR96 [97] and Hu3S19 [98], both of which target Ley, have been developed in the past. However, these antibodies have failed to show significant anti-tumor responses. In ovarian cancer, the mAb PankoMab-GEX (gatipotuzumab) designed to target tumor-associated MUC1, has shown mixed results with earlier trials showing significantly improved outcome [99,100], while a follow-up phase II clinical trial did not show any therapeutic efficacy. Finally, a mAb targeting the Tn glycoform of mucin MUC1 has been shown to promote ADCC and CDC in breast cancer cells [101].