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456. Pharmacodynamics and GMP Development of a Lentivirus-Induced DC Vaccine for Accelerated Adaptive Immune Reconstitution Against Cytomegalovirus after Stem Cell Transplantation
- Source :
- Molecular Therapy. 23
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Effective immunization of patients shortly after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an unmet clinical need due to delayed de novo development of T and B cells. We demonstrated a recombinant, donor-derived cell vaccine against cytomegalovirus that can be easily manufactured, cryopreserved and, upon thaw and administration, turn themselves into highly-viable dendritic cells (DCs). The cell source consisted of monocytes from peripheral blood or cord blood (CB), transduced with an integrase-defective lentiviral vector (IDLV, co-expressing GM-CSF, IFN-α and the cytomegalovirus antigen pp65). The pharmacodynamics of the frozen/thawed vaccine (“SmyleDCpp65”) was evaluated by immunization of NOD.Rag1–/–.IL2rγ–/– mice transplanted with human CD34+ CB stem cells. SmyleDCpp65 stimulated in vivo thymic and extrathymic expansion of human cytotoxic T cells (CTL) reactive against pp65, and high levels of human immunoglobulins and immune-stimulatory cytokines in plasma. Standardized production of the IDLV and SmyleDCpp65 was established using Good Manufacturing Practices (GMP). Analytical parameters for quality control demonstrated high recovery, uniformity, purity and viability of SmyleDCpp65 after thawing. Stimulation of autologous T cells by GMP-grade SmyleDCpp65 was validated. SmyleDCpp65 showed only residual and polyclonal IDLV integration, unbiased to protooncogenic hot-spots. These results underscore further developments of this individualized cell vaccine to accelerate immune reconstitution against cytomegalovirus after allo-HSCT.
- Subjects :
- Pharmacology
medicine.medical_treatment
Congenital cytomegalovirus infection
Hematopoietic stem cell transplantation
Biology
medicine.disease
Virology
Viral vector
Transplantation
Immune system
Cord blood
Immunology
Drug Discovery
medicine
Genetics
Cytotoxic T cell
Molecular Medicine
Stem cell
Molecular Biology
Subjects
Details
- ISSN :
- 15250016
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy
- Accession number :
- edsair.doi.dedup.....105699091a3f22dc6a36357abe2e957b
- Full Text :
- https://doi.org/10.1016/s1525-0016(16)34065-5