The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen recognizing receptor and one of a chimeric costimulatory receptor. Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Glycopeptides derived from short CD44 isoforms lacking amino acids encoded by exons 6-14; presenting one or multiple serine or threonine residues substituted with Tn (GalNAc-O-Ser/Thr) and/or sialyl-Tn (STn; Neu5Ac2-6GalNAc-O-Ser/Thr) antigens. Synthesizing the glycopeptides, including one-pot glycosylation of synthetic short isoform CD44 peptides through combination with nucleotide sugars and glycosyltransferases and purification of CD44s-Tn glycopeptides. Immunogenic chimeras derived from the CD44-Tn and/or STn glycopeptides, linked, in polyvalent form, to a carrier immunogenic protein, e.g., KLH CRM197. Conjugating the synthesized CD44s-Tn glycopeptides to the immunogenic protein carriers CRM197 and KLH, generating chimeric glycopeptides, termed CRM197-CD44s-Tn and KLH-CD44s-Tn. CD44-Tn/STn glycopeptides or compositions thereof for treating cancer and pre-neoplastic diseases, e.g., neoplastic diseases expressing short CD44 isoforms, through generating antibodies against cancer cells and treating/preventing cancer by vaccination. The glycopeptides, compositions, synthesis methods and uses can be employed in treating cancer, alone or in combination with immune checkpoint inhibitor therapy, chemotherapy, and radiotherapy.