Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma - A phase 1 study

S. Trudel, Z. Li, C. Dodgson, S. Nanji, Y. Wan, M. Voralia, M. Hitt, J. Gauldie, F. L. Graham, Alexander Keith Stewart

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Eight multiple myeloma patients participated in a phase 1 trial evaluating the feasibility and safety of subcutaneous vaccination with adenovirus engineered, autologous plasma cells after high-dose therapy. Plasma cells were concentrated from bone marrow harvests by negative selection and high gradient magnetic separation. The mean plasma cell yield was 2.61 × 108. Transgene expression measured 48 h after plasma cell infection with an IL-2 expressing adenovirus averaged 2.95 ng/ml/106 cells. Vaccine production was successful for 88% of patients. Two months after high-dose therapy, six patients received from one to five injections of 3.5-9.0 × 107 cells/vaccine. Vaccines were well tolerated with only minor systemic symptoms reported. Injection with tumor cells induced a local inflammatory response consisting predominantly of CD8+ and/or TIA-1+ T-lymphocytes. Myeloma specific anti-tumor responses, assessed by interferon-γ (IFN-γ) release and cytotoxic T cell killing of autologous tumor cells, were not enhanced after vaccination in one evaluable patient. Clinical response, manifested as a decrease in serum paraprotein, was not observed in the one patient who had measurable disease at the time of vaccination. These results demonstrate that the generation of adenovector modified plasma cell vaccines is technically feasible and can be safely administered post-transplant. Further studies of immunlogic and clinical efficacy are required.

Original languageEnglish (US)
Pages (from-to)846-854
Number of pages9
JournalLeukemia
Volume15
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Plasma Cells
Multiple Myeloma
Interleukin-2
Vaccination
Drug Therapy
Vaccines
Adenoviridae
Paraproteins
T-Lymphocytes
Neoplasms
Injections
Transgenes
Interferons
Bone Marrow
Transplants
Safety
Therapeutics
Infection
Serum

Keywords

  • Gene therapy
  • IL-2
  • Multiple myeloma
  • Vaccination

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma - A phase 1 study. / Trudel, S.; Li, Z.; Dodgson, C.; Nanji, S.; Wan, Y.; Voralia, M.; Hitt, M.; Gauldie, J.; Graham, F. L.; Stewart, Alexander Keith.

In: Leukemia, Vol. 15, No. 5, 2001, p. 846-854.

Research output: Contribution to journalArticle

Trudel, S. ; Li, Z. ; Dodgson, C. ; Nanji, S. ; Wan, Y. ; Voralia, M. ; Hitt, M. ; Gauldie, J. ; Graham, F. L. ; Stewart, Alexander Keith. / Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma - A phase 1 study. In: Leukemia. 2001 ; Vol. 15, No. 5. pp. 846-854.
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