A pilot Phase I study combining peptide-based vaccination and NGR-hTNF vessel targeting therapy in metastatic melanoma

Giorgio Parmiani, Lorenzo Pilla, Angelo Corti, Claudio Doglioni, Carolina Cimminiello, Matteo Bellone, Danilo Parolini, Vincenzo Russo, Filippo Capocefalo, Cristina Maccalli

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Administration of NGR-TNF, a tumor vessel-targeting and tumor necrosis factor α TNFα) peptide conjugate, with immunotherapy has been shown to inhibit tumor growth in mice. Thus, we planned a Phase I pilot clinical trial to assess safety, immune and clinical response of this combination treatment for advanced melanoma. NA17.A2 and MAGE-3.A1 peptides were used as vaccine. HLA-A*0201 or HLA-A*01 metastatic melanoma patients received human NGR-hTNF i.v. alternating with s.c. weekly injections of either of the peptides emulsified in Montanide. The T-cell response was assessed ex-vivo using peripheral blood mononuclear cells (PBMCs) before, during and after therapy. The serum level of chromogranin A (CgA), soluble TNF receptors (sTNFR1/2), vascular endothelial growth factor (VEGF), and MIP-1β and MCP-1 chemokines, was determined. In 3 subjects, pre- and post-treatment tumor lesions were examined by immunohistochemistry. Clinically, chills were observed in 4 patients during NGR-hTNF infusion and erythema at vaccination site was seen in 7 patients. T-cell response against the vaccine or against other melanoma-associated antigens was detectable after treatment in 6 out of 7 tested patients. Low level or reduction of CgA and sTNFR and increase of MIP-1β and MCP-1 were found in patients sera. In the lesions examined the immune infiltrate was scanty but macrophage number increased in post-therapy lesions. From a clinical standpoint, a long term survival (>4 months) was found in 6 out of 8 evaluable patients (4, 4, 7, 11, 23C, 25C, 25C, 29C months). The combination of NGR-hTNF and vaccine in metastatic melanoma patients was well tolerated, often associated with an ex-vivo T cell response and longterm overall survival. These findings warrant confirmation in a larger group of patients.

Original languageEnglish
Pages (from-to)e963406-1-e963406-6
JournalOncoImmunology
Volume3
Issue number11
DOIs
Publication statusPublished - 2 Nov 2014
Externally publishedYes

    Fingerprint

Keywords

  • anti-vascular target therapy
  • combination therapy
  • inflammatory cytokines
  • melanoma
  • peptide-based vaccines
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Parmiani, G., Pilla, L., Corti, A., Doglioni, C., Cimminiello, C., Bellone, M., Parolini, D., Russo, V., Capocefalo, F., & Maccalli, C. (2014). A pilot Phase I study combining peptide-based vaccination and NGR-hTNF vessel targeting therapy in metastatic melanoma. OncoImmunology, 3(11), e963406-1-e963406-6. https://doi.org/10.4161/21624011.2014.963406