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

• DOI: 10.1111/bjh.13245
• Publication Date: 2014-12-11T11:41:37Z
• Authors: Lior Carmon; Irit Avivi; Riva Kovjazin; Tsila Zuckerman; Lillian Dray; Moshe E. Gatt; Reuven Or; Michael Y. Shapira
• Keywords: CD4-Positive T-Lymphocytes; Male; 0301 basic medicine; Mucin-1; Vaccination; Epitopes, T-Lymphocyte; CD8-Positive T-Lymphocytes; Middle Aged; Protein Sorting Signals; Cancer Vaccines; B7-H1 Antigen; 3. Good health; Interferon-gamma; 03 medical and health sciences; Epitopes, B-Lymphocyte; Humans; Female; Multiple Myeloma; Aged; Cell Proliferation

SummaryImMucin, 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.