title: Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients.
abstract: 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. ImMucin vaccination induced a robust increase in γ-interferon (IFN-γ-producing CD4+ and CD8+ T-cells (≤80-fold), a pronounced population of ImMucin multimer CD8+ T-cells (>2%), a 9·4-fold increase in peripheral blood mononuclear cells proliferation and 6·8-fold increase in anti-ImMucin antibodies, accompanied with T-cell and antibody-dependent cell-mediated cytotoxicity. A significant decrease in soluble MUC1 levels was observed in 9/10 patients. Stable disease or improvement, persisting for 17·5-41·3 months (ongoing) was achieved in 11/15 patients and appeared to be associated with low-intermediate PDL1 (CD274) bone marrow levels pre- and post-vaccination. In summary, ImMucin, a highly tolerable cancerous vaccine, induces robust, diversified T- and B-cell ImMucin-specific immunity in MM patients, across major histocompatibility complex-barrier, resulting in at least disease stabilization in most patients.
authors.affiliation: Vaxil BioTherapeutics Ltd., Nes-Ziona, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Carmon
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.forename: Riva
authors.initials: R
authors.lastname: Kovjazin
authors.forename: Tsila
authors.initials: T
authors.lastname: Zuckerman
authors.forename: Lillian
authors.initials: L
authors.lastname: Dray
authors.forename: Moshe E
authors.initials: ME
authors.lastname: Gatt
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shapira
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000008:administration & dosage* / Q000276:immunology; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D021382:Protein Sorting Signals; D014611:Vaccination
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; C573415:IFNG protein, human; C060192:MUC1 protein, human; D018396:Mucin-1; D021382:Protein Sorting Signals; D007371:Interferon-gamma
keywords: ImMucin; MUC1; cancer vaccine; multiple myeloma; signal peptide