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Complete molecular remissions induced by patient-specific vaccination plus granulocyte–monocyte colony-stimulating factor against lymphoma

Nature Medicine volume 5, pages 1171–1177 (1999)Cite this article

Abstract

Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14;18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8+ and CD4+ T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte–monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting.

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Figure 1: PCR sensitivity and optimization.
Figure 2: Monitoring of minimal residual disease in the peripheral blood.
Figure 3: Vaccine-induced, tumor-specific PBMC cytokine (TNF) responses.
Figure 4: Cytotoxicity against unmodified, Au FL cells.

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Acknowledgements

We thank the physicians and nursing staff of the former Biological Response Modifiers Program and the pharmacy and nursing staff of the 13E unit in building 10, NIH Clinical Center, for their patient care. We also thank S. Grove, J. Mikovits and C. Petrow for technical assistance and D. D. Taub for scientific discussions.

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Authors and Affiliations

  1. Department of Experimental Transplantation and Immunology Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland, USA

    Maurizio Bendandi, Lars A. Sternas, Thelma M. Watson, Barry L. Gause & Larry W. Kwak

  2. Division of Cancer Treatment and Diagnosis, Biological Resources Branch, National Cancer Institute, Bethesda, Maryland, USA

    Craig W. Reynolds & Stephen P. Creekmore

  3. Laboratory of Pathology, National Cancer Institute , Bethesda, Maryland, USA

    Elaine S. Jaffe

  4. Department of Pathology, Pennsylvania State University, Hershey, Pennsylvania, USA

    Christopher D. Gocke & Floyd A. Benko

  5. Science Applications International Corporation, Frederick, Maryland, USA

    Carol B. Kobrin & Robin Pennington

  6. National Institute on Aging, NIH Gerontology Research Center, Baltimore, Maryland, USA

    Patricia L. Duffey & Dan L. Longo

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  1. Maurizio Bendandi
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  14. Larry W. Kwak
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Correspondence to Larry W. Kwak.

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Bendandi, M., Gocke, C., Kobrin, C. et al. Complete molecular remissions induced by patient-specific vaccination plus granulocyte–monocyte colony-stimulating factor against lymphoma . Nat Med 5, 1171–1177 (1999). https://doi.org/10.1038/13928

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