Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant

Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the saf...

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Published in:Blood advances Vol. 6; no. 5; pp. 1547 - 1558
Main Authors: Chung, David J., Sharma, Sneh, Rangesa, Madhumitha, DeWolf, Susan, Elhanati, Yuval, Perica, Karlo, Young, James W.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 08.03.2022
American Society of Hematology
Subjects:
Antigens, Neoplasm
Autografts
Cancer Vaccines - adverse effects
Clinical Trials and Observations
Dendritic Cells
Hematopoietic Stem Cell Transplantation
Humans
Lenalidomide
Multiple Myeloma
RNA, Messenger - genetics
Transplantation, Autologous
ISSN:2473-9529, 2473-9537, 2473-9537
Online Access:Get full text
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Summary:Posttransplant vaccination targeting residual disease is an immunotherapeutic strategy to improve antigen-specific immune responses and prolong disease-free survival after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We conducted a phase 1 vaccine trial to determine the safety, toxicity, and immunogenicity of autologous Langerhans-type dendritic cells (LCs) electroporated with CT7, MAGE-A3, and Wilms tumor 1 (WT1) messenger RNA (mRNA), after ASCT for MM. Ten patients received a priming immunization plus 2 boosters at 12, 30, and 90 days, respectively, after ASCT. Vaccines contained 9 × 106 mRNA-electroporated LCs. Ten additional patients did not receive LC vaccines but otherwise underwent identical ASCT and supportive care. At 3 months after ASCT, all patients started lenalidomide maintenance therapy. Vaccinated patients developed mild local delayed-type hypersensitivity reactions after booster vaccines, but no toxicities exceeded grade 1. At 1 and 3 months after vaccines, antigen-specific CD4 and CD8 T cells increased secretion of proinflammatory cytokines (interferon-γ, interleukin-2, and tumor necrosis factor-α) above prevaccine levels, and also upregulated the cytotoxicity marker CD107a. CD4 and CD8 T-cell repertoire analysis showed a trend for increased clonal expansion in the vaccine cohort, which was more pronounced in the CD4 compartment. Although not powered to assess clinical efficacy, treatment responses favored the vaccine arm. Triple antigen–bearing mRNA-electroporated autologous LC vaccination initiated at engraftment after ASCT, in conjunction with standard lenalidomide maintenance therapy for MM, is safe and induces antigen-specific immune reactivity. This trial was registered at www.clinicaltrials.gov as #NCT01995708. •Triple antigen–bearing mRNA-electroporated autologous LC vaccines after ASCT for MM are safe and immunogenic. [Display omitted]
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Requests for data sharing may be submitted to  David J. Chung (chungd1@mskcc.org).
ISSN:2473-9529
2473-9537
2473-9537
DOI:10.1182/bloodadvances.2021005941