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A 15-Year Follow-up of AJCC Stage III Malignant Melanoma Patients Treated Postsurgically with Newcastle Disease Virus (NDV) Oncolysate and Determination of Alterations in the CD8 T Cell Repertoire

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Abstract

Background

The development of effective adjuvant therapies for the treatment of high-risk melanoma patients is critical for the prevention of metastatic disease and improvement of patient survival. Active specific immunotherapy has been tested as an adjuvant treatment in numerous clinical trials with overall limited, but occasionally promising, success rates. Newcastle disease virus (NDV) oncolysate has been utilized as an adjunctive immunotherapeutic agent in the postsurgical management of these patients. A phase II study initiated in 1975 using adjuvant vaccine therapy composed of allogeneic and autologous human melanoma cells infected with live NDV (NDV oncolysate) in patients with AJCC stage III melanoma following therapeutic lymph node dissection has shown >60% survival rate at 10 years with no adverse effects. Continued long-term analysis of trials with promising early results as well as assessment of immunologic responses generated in these patients may result in improved therapeutic decisions for clinical trials in the future.

Materials and Methods

We analyzed the 15-year survival of patients treated postsurgically with NDV oncolysate in the phase II study described above. In an attempt to understand the immunological effects of this treatment, we have also carried out a comprehensive analysis of the peripheral blood T cell repertoire in these patients.

Results

The overall 15-year survival of this group of patients is 55%. Previous studies have suggested that improved outcome in patients undergoing immunotherapy is correlated with increased numbers of CD8+CD57+ cells. In surviving patients, we observed a striking oligoclonality in the CD8+ T cell population in peripheral blood, which reflects clonal expansions in the CD8+CD57+ subset.

Conclusions

The data suggest that adjuvant vaccination with NDV oncolysates is associated with prolonged survival of patients with lymph node-positive malignant melanoma and that CD8+ T cells may be an important component of therapeutic efficacy.

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Acknowledgments

The authors thank Ms. Catherine Rapelje and Ms. Grace Lee for assistance with flow cytometric data acquisition, as well as Dr. Christina Sison and Mr. Robert Greenlee for assistance with bio-statistical analysis.

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Author notes

  1. Stuart Macphail

    Present address: Fish and Richardson, 45 Rockefeller Plaza, New York, NY, 10111, USA

Authors and Affiliations

  1. Department of Medicine, North Shore University Hospital-NYU School of Medicine, 350 Community Drive, Manhasset, New York, 11030, USA

    Franak M. Batliwalla, Davide Serrano, Stuart Macphail &  Peter K. Gregersen

  2. Department of Dermatology, Emory University School of Medicine, 5001 Woodruff Memorial Building, Atlanta, Georgia, 30322, USA

    Barbara A. Bateman, John C. Ansel &  Cheryl A. Armstrong

  3. Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA

    Douglas Murray

  4. Veterans Affairs Medical Center, Atlanta, Georgia, USA

    John C. Ansel &  Cheryl A. Armstrong

  5. Becton Dickinson, Qume Drive, San Jose, California, USA

    V. C. Maino

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  1. Franak M. Batliwalla
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Correspondence to Peter K. Gregersen or Cheryl A. Armstrong.

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Batliwalla, F.M., Bateman, B.A., Serrano, D. et al. A 15-Year Follow-up of AJCC Stage III Malignant Melanoma Patients Treated Postsurgically with Newcastle Disease Virus (NDV) Oncolysate and Determination of Alterations in the CD8 T Cell Repertoire. Mol Med 4, 783–794 (1998). https://doi.org/10.1007/BF03401771

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