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Phase I/II study exploring ImMucin, a pan-major histocompatibility complex, anti-MUC1 signal peptide vaccine, in multiple myeloma patients.
- Source :
-
British journal of haematology [Br J Haematol] 2015 Apr; Vol. 169 (1), pp. 44-56. Date of Electronic Publication: 2014 Dec 11. - Publication Year :
- 2015
-
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.<br /> (© 2014 John Wiley & Sons Ltd.)
- Subjects :
- Aged
B7-H1 Antigen blood
B7-H1 Antigen immunology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes metabolism
CD4-Positive T-Lymphocytes pathology
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes pathology
Cancer Vaccines immunology
Cancer Vaccines pharmacology
Cell Proliferation drug effects
Epitopes, B-Lymphocyte immunology
Epitopes, T-Lymphocyte immunology
Female
Humans
Interferon-gamma blood
Interferon-gamma immunology
Male
Middle Aged
Mucin-1 immunology
Multiple Myeloma blood
Multiple Myeloma immunology
Cancer Vaccines administration & dosage
Epitopes, B-Lymphocyte administration & dosage
Epitopes, T-Lymphocyte administration & dosage
Mucin-1 administration & dosage
Multiple Myeloma drug therapy
Protein Sorting Signals
Vaccination
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 169
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 25496030
- Full Text :
- https://doi.org/10.1111/bjh.13245