CD44 GLYCOEPITOPES AND CHIMERIC VACCINE GLYCOCONJUGATES FOR CANCER THERAPY AND SYNTHESIS METHODS THEREOF

The present invention refers to glycopeptides derived from the short CD44 isoforms lacking the amino acids encoded by exons 6-14, the said glycopeptides presenting at least one or multiple serine or threonine residues substituted with Tn ( GalNAca-O-Ser/Thr ) and/or sialyl-Tn (STn; Neu5Aca2-6GalNAca-O-Ser/Thr) antigens. The present invention further provides a method for synthesizing the herein disclosed glycopeptides, the said method comprising a one-pot glycosylation of synthetic short isoform CD44 peptides through combination with nucleotide sugars and glycosyl trans f erases and subsequent purification of the CD44s-Tn glycopeptides by lectin affinity chromatography followed by Ti02 chromatography or liquid chromatography. In one embodiment, the present invention further comprises immunogenic chimeras derived from the said CD44-Tn and/or STn glycopeptides, which are linked, in a polyvalent form, to a carrier immunogenic protein, such as keyhole limpet hemocyanin (KLH) or cross-reacting material (CRM197). Methods for conj ugating the synthesized CD44s-Tn glycopeptides to the immunogenic protein carriers CRM197 and KLH, are described, generating the chimeric glycopeptides, herein termed CRM197 -CD44 s-Tn and KLH-CD44s-Tn, respectively. The present invention further regards the above-mentioned CD44-Tn/STn glycopeptides or compositions comprising said glycopeptides for use in the treatment of cancer and pre-neoplastic diseases, most preferably of neoplastic diseases expressing short CD44 isoforms, through generation of antibodies against cancer cells and treatment and prevention of cancer by vaccination. The glycopeptides, compositions, synthesis methods and uses of the present invention can be advantageously employed in the treatment of cancer, alone or in combination with immune checkpoint inhibitor therapy, chemotherapy, and radiotherapy.