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Local and Distant Immunity Induced by Intralesional Vaccination with an Oncolytic Herpes Virus Encoding GM-CSF in Patients with Stage IIIc and IV Melanoma

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

An oncolytic herpes simplex virus engineered to replicate selectively in tumor cells and to express granulocyte–macrophage colony-stimulating factor (GM-CSF) was tested as a direct intralesional vaccination in melanoma patients. The work reported herein was performed to better characterize the effect of vaccination on local and distant antitumor immunity.

Methods

Metastatic melanoma patients with accessible lesions were enrolled in a multicenter 50-patient phase II clinical trial of an oncolytic herpesvirus encoding GM-CSF (OncovexGM-CSF). An initial priming dose of 106 pfu vaccine was given by intratumoral injection, followed by 108 pfu every 2 weeks to 24 total doses. Peripheral blood and tumor tissue were collected for analysis of effector T cells, CD4+FoxP3+ regulatory T cells (Treg), CD8+FoxP3+ suppressor T cells (Ts), and myeloid-derived suppressive cells (MDSC).

Results

Phenotypic analysis of T cells derived from tumor samples suggested distinct differences from peripheral blood T cells. There was an increase in melanoma-associated antigen recognized by T cells (MART-1)-specific T cells in tumors undergoing regression after vaccination compared with T cells derived from melanoma patients not treated with vaccine. There was also a significant decrease in Treg and Ts cells in injected lesions compared with noninjected lesions in the same and different melanoma patients. Similarly MDSC were increased in melanoma lesions but underwent a significant decrease only in vaccinated lesions.

Conclusions

Melanoma patients present with elevated levels of Tregs, Ts, and MDSC within established tumors. Direct injection of OncovexGM-CSF induces local and systemic antigen-specific T cell responses and decreases Treg, Ts, and MDSC in patients exhibiting therapeutic responses.

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Financial Disclosure

Rob Coffin is employed by and has stock options in Biovex, Inc. the manufacturer of the vaccine used in this manuscript.

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Authors and Affiliations

  1. Department of Surgery, Medicine and Immunology, Rush University Medical Center, Chicago, IL, USA

    Howard L. Kaufman MD & Dae Won Kim MD

  2. The Tumor Immunology Laboratory, Department of Surgery, Mount Sinai School of Medicine, New York, NY, USA

    Gail DeRaffele RN, Josephine Mitcham BS & Seunghee Kim-Schulze PhD

  3. Biovex, Inc., Cambridge, MA, USA

    Rob S. Coffin PhD

Authors
  1. Howard L. Kaufman MD
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  2. Dae Won Kim MD
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  3. Gail DeRaffele RN
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  4. Josephine Mitcham BS
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  5. Rob S. Coffin PhD
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  6. Seunghee Kim-Schulze PhD
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Correspondence to Howard L. Kaufman MD.

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Kaufman, H.L., Kim, D.W., DeRaffele, G. et al. Local and Distant Immunity Induced by Intralesional Vaccination with an Oncolytic Herpes Virus Encoding GM-CSF in Patients with Stage IIIc and IV Melanoma. Ann Surg Oncol 17, 718–730 (2010). https://doi.org/10.1245/s10434-009-0809-6

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  • DOI: https://doi.org/10.1245/s10434-009-0809-6

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