Dendritic cell-based idiotype vaccination for primary systemic amyloidosis

M. Q. Lacy, P. Wettstein, A. Dispenzieri, D. A. Gastineau, P. R. Greipp, R. Fonseca, J. Lust, T. Witzig, S. V. Rajkumar, F. Valone, R. A. Kyle, M. A. Gertz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Introduction: A clinical trial of dendritic cell-based idiotype (id) vaccination as therapy for primary systemic amyloidosis (AL) was undertaken. Methods: Patients with AL were eligible whether or not they were previously treated. Following leukopheresis, dendritic cell (DC) precursors were partially purified from the peripheral blood mononuclear cells by gradient density isolation. The DCs were incubated ex vivo with serum containing id diluted to 10 meg/ml. After two days of culture the antigen-loaded DCs and accompanying T lymphocytes, designated APC8020, were infused into the patient. Patients underwent repeat vaccinations in weeks 2, 4, and 16, Peripheral blood lymphocytes were collected at baseline and in weeks 8, 16, and 32 for assessment of immunologie responses including 1) peripheral blood lymphocyte phenotyping by FACS analysis; 2) T cell proliferation to phytohemagglutinin (PHA); 3) T cell proliferation to id with controls consisting of T cell proliferation to tetanus toxoid and to commercially available class-matched normal immunoglobulin. Results: Ten patients were enrolled between 9/98 and 6/2000. Organ involvement included: cardiac (2), pulmonary (1), renal (6), liver (2) neuropathy (3) gastrointestinal tract (2) Five had multiorgan involvement. Previous therapies included: none (2), corticosteroids (2), chemotherapy (3) and stem cell transplant (3). Associated M-proteins included: GK (1). GX. (5), MK (2), MX. (1) and AX (1). No toxicity was seen. One patient developed an objective response improvement in her proteinuria (1.4 to 0.057 gm/24°). One patient experienced dramatic improvement of a painful peripheral neuropathy despite no objective response. Three patients developed progressive amyloidosis and two have died. The remainder have been clinically stable including four who are 18 months after enrollment. Laboratory immunologie correlates showed decreased number and function of T cells including both the CD4+ and the CD8+ populations. Specific T cell proliferative responses to id were detectable in the patient who developed a clinical response. Conclusions: DC vaccination with id is clinically feasible and safe. Early clinical results appear promising. Future studies will be directed at optimizing immune function and response to vaccines.

Original languageEnglish (US)
Pages (from-to)164a
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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