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

Lior Carmon, Irit Avivi, Riva Kovjazin, Tsila Zuckerman, Lillian Dray, Moshe E. Gatt, Reuven Or, Michael Y. Shapira

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: 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.

Original languageEnglish
Pages (from-to)44-56
Number of pages13
JournalBritish Journal of Haematology
Volume169
Issue number1
DOIs
StatePublished - 1 Apr 2015
Externally publishedYes

Keywords

  • Cancer vaccine
  • ImMucin
  • MUC1
  • Multiple myeloma
  • Signal peptide

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