Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients.

ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumour-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This phase I/II study assessed the safety, immunity and clinical response to 6 or 12 bi-weekly intradermal ImMucin vaccines, co-administered with human granulocyte-macrophage colony-stimulating factor to 15 MUC1-positive multiple myeloma (MM) patients, with residual or biochemically progressive disease following autologous stem cell transplantation. Vaccination was well tolerated; all adverse events were temporal grade 1 2 and spontaneously resolved.

The use of signal peptide domains as vaccine candidates.

Signal peptide (SP) domains have a common motif but also sequence specific features. This knowledge was mainly ignored by immunologists who considered SP as generic, short-lived, targeting sequences. Consequently, while SP-derived MHC class I, class II and HLA-E epitopes have been isolated, their use as antigen-specific vaccine candidates (VCs) was mostly neglected.

Cell surface-associated anti-MUC1-derived signal peptide antibodies: implications for cancer diagnostics and therapy.

The MUC1 tumor associated antigen is highly expressed on a range of tumors. Its broad distribution on primary tumors and metastases renders it an attractive target for immunotherapy. After synthesis MUC1 is cleaved, yielding a large soluble extracellular alpha subunit containing the tandem repeats array (TRA) domain specifically bound, via non-covalent interaction, to a smaller beta subunit containing the transmembrane and cytoplasmic domains.

Characterization of novel multiantigenic vaccine candidates with pan-HLA coverage against Mycobacterium tuberculosis.

The low protection by the bacillus Calmette-Guérin (BCG) vaccine and existence of drug-resistant strains require better anti-Mycobacterium tuberculosis vaccines with a broad, long-lasting, antigen-specific response. Using bioinformatics tools, we identified five 19- to 40-mer signal peptide (SP) domain vaccine candidates (VCs) derived from M. tuberculosis antigens.

Autoantibodies against the signal peptide domain of MUC1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis.

Naturally generated autoantibodies to tumor-associated antigens such as MUC1 can assist in cancer diagnosis and prognosis. While previous studies have concentrated on the tandem repeat array domain of MUC1, here we focused on MUC1's signal peptide domain. We used ELISA assays with MUC1-specific epitopes and antibodies to quantify soluble MUC1 antigen and anti-MUC1 autoantibodies against the tandem repeat array and signal peptide domains in 15 naïve donors and 27 multiple myeloma cancer patients.