{"database":"panorama","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["John Koomen"],"species":["Homo Sapiens"],"full_dataset_link":["https://panoramaweb.org/QacsTA.url"],"submitter_email":["john.koomen@moffitt.org"],"submitter_affiliation":["Moffitt Cancer Center"],"sample_protocol":[""],"repository":["PanoramaPublic"],"data_protocol":[""],"pubmed_abstract":["Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied the ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific dIgA, but not IgG, neutralized KRAS<sup>G12D</sup> within ovarian carcinoma cells and expelled this oncodriver from tumor cells. dIgA binding changed endosomal trafficking of KRAS<sup>G12D</sup> from accumulation in recycling endosomes to aggregation in the early/late endosomes through which dIgA transcytoses. dIgA targeting of KRAS<sup>G12D</sup> abrogated tumor cell proliferation in cell culture assays. In vivo, KRAS<sup>G12D</sup>-specific dIgA1 limited the growth of KRAS<sup>G12D</sup>-mutated ovarian and lung carcinomas in a manner dependent on CD8<sup>+</sup> T cells. dIgA specific for IDH1<sup>R132H</sup> reduced colon cancer growth, demonstrating effective targeting of a cytoplasmic oncodriver not associated with surface receptors. dIgA targeting of KRAS<sup>G12D</sup> restricted tumor growth more effectively than small-molecule KRAS<sup>G12D</sup> inhibitors, supporting the potential of this approach for the treatment of human cancers."],"pubmed_title":["Targeting intracellular oncoproteins with dimeric IgA promotes expulsion from the cytoplasm and immune-mediated control of epithelial cancers."],"pubmed_authors":["Biswas Subir S, Mandal Gunjan G, Anadon Carmen M CM, Chaurio Ricardo A RA, Lopez-Bailon Luis U LU, Nagy Mate Z MZ, Mine Jessica A JA, Hänggi Kay K, Sprenger Kimberly B KB, Innamarato Patrick P, Harro Carly M CM, Powers John J JJ, Johnson Joseph J, Fang Bin B, Eysha Mostafa M, Nan Xiaolin X, Li Roger R, Perez Bradford A BA, Curiel Tyler J TJ, Yu Xiaoqing X, Rodriguez Paulo C PC, Conejo-Garcia Jose R JR"],"additional_accession":[]},"is_claimable":false,"name":"Dimeric IgA specifically disables intracellular mutated oncodrivers","description":"Despite their long half-life, therapeutic antibodies are considered ineffective against intracellular antigens due to their perceived inability to penetrate epithelial cells. Using recombinant antibodies targeting common mutations in oncogenes, we demonstrate that dimeric IgA, but not the same antibody on an IgG backbone, penetrates human epithelial cancer cells through PIGR-dependent directional transcytosis, specifically neutralizing mutated oncodrivers and expelling antigens outside the cell, bound to secretory IgA. Accordingly, targeting of KRASG12D or IDH1R132H with antigen-specific dimeric IgA abrogated the growth of different carcinomas in a mutation-specific manner, including in syngeneic tumor-bearing immunocompetent mice. Our results provide a rationale for developing PIGR-targeting tumor cell-penetrating antibodies to effectively target common mutations in intracellular oncogenes that drive many aggressive and frequent human cancers.","dates":{"publication":"Fri Jun 12 00:00:00 GMT+01:00 2026"},"accession":"PXD044426","cross_references":{"TAXONOMY":["9606"],"pubmed":["37909039"]}}