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Phase I/ II study exploring ImMucin, a pan‐major histocompatibility complex, anti‐ MUC 1 signal peptide vaccine, in multiple myeloma patients
Author(s) -
Carmon Lior,
Avivi Irit,
Kovjazin Riva,
Zuckerman Tsila,
Dray Lillian,
Gatt Moshe E.,
Or Reuven,
Shapira Michael Y.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13245
Subject(s) - immunology , cd8 , medicine , population , t cell , antigen , antibody , cytotoxic t cell , peripheral blood mononuclear cell , immune system , biology , biochemistry , environmental health , in vitro
Summary ImMucin, a 21‐mer cancer vaccine encoding the signal peptide domain of the MUC 1 tumour‐associated antigen, possesses a high density of T‐ and B‐cell epitopes but preserves MUC 1 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 MUC 1‐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 CD 4+ and CD 8+ T‐cells (≤80‐fold), a pronounced population of ImMucin multimer CD 8+ 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 MUC 1 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 PDL 1 ( CD 274) 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.