| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Article |
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, at the University of South Florida, Tampa, FL, USA
Correspondence: Address correspondence and reprint requests to: Sophie Dessureault, H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA; E-mail: dessursm{at}moffitt.usf.edu
Background: Significant antitumor T-cell responses are generated in vitro when human lymphocytes are stimulated with autologous tumor cells in the presence of bystander cells transfected with CD40L and GM-CSF. Our goal was to test this bystander-based vaccine strategy in vivo in cancer patients with stage IV disease.
Methods: Patients received three intradermal vaccine injections (irradiated autologous tumor cells plus GM.CD40L bystander cells) at 28-day intervals. Patients with no disease progression received three additional vaccines at 4, 12, and 24 months. Patients were monitored for toxicity, tumor response, and tumor-specific immune responses.
Results: Twenty-one patients received at least three vaccine injections, with no toxicity attributable to the vaccine. Immunohistochemistry of vaccine injection site biopsies with CD1a and CD86 antibodies confirmed recruitment and activation of dendritic cells. There was no tumor regression after vaccination, but many patients had stable disease, including six of ten melanoma patients. Four patients developed tumor-specific T-cell responses on ELISPOT testing. One patient, who had stable disease for 24 months, demonstrated an increase in MART-1-specific T-cells by tetramer analysis after re-immunization; biopsy of the tumor that progressed 2 years after the onset of vaccination revealed a massive peritumoral and intratumoral T-cell infiltrate.
Conclusions: Vaccination of cancer patients with autologous tumor cells and GM.CD40L bystander cells (engineered to express GM-CSF and CD40L) is safe, can recruit and activate dendritic cells, and can elicit tumor-specific T-cell responses. Phase-II trials are underway to evaluate the impact of bystander-based vaccines on melanoma and mantle cell lymphoma.
Key Words: cancer vaccine • immunotherapy • phase-I clinical trial • bystander • CD40 ligand • GM-CSF
Abbreviations: APC, antigen-presenting cell • CD40L, CD40 ligand • DC, dendritic cell • DTH, delayed-type hypersensitivity • ELISA, enzyme-linked immunosorbent assay • GM-CSF, granulocyte macrophage-colony stimulating factor • IL, interleukin • MIP-1, monocyte inflammatory protein-1 • MRD, minimal residual disease • PBMC, peripheral blood mononuclear cell • RECIST, Response Evaluation Criteria in Solid Tumors • TAA, tumor-associated antigen
This article has been cited by other articles:
 |
|
 |
|
  A. Kobayashi, C. Pulitano, G. Liddo, and N. Ohkohchi The Growing Evidence of the Role of T-Cells in the Treatment of Solid Tumors Ann. Surg. Oncol., April 1, 2008; 15(4): 1254 - 1254. [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Ryan, T. M. Wozniak, E. Shklovskaya, M. A. O'Donnell, B. Fazekas de St. Groth, W. J. Britton, and J. A. Triccas Improved Protection against Disseminated Tuberculosis by Mycobacterium bovis Bacillus Calmette-Guerin Secreting Murine GM-CSF Is Associated with Expansion and Activation of APCs J. Immunol., December 15, 2007; 179(12): 8418 - 8424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Neelapu and L. W. Kwak Vaccine Therapy for B-Cell Lymphomas: Next-Generation Strategies Hematology, January 1, 2007; 2007(1): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
