Therapy-induced antitumor vaccination by targeting tumor necrosis factor-α to tumor vessels in combination with melphalan

Lorenzo Mortara, Enrica Balza, Francesca Sassi, Patrizia Castellani, Barbara Carnemolla, Andrea De Lerma Barbaro, Sara Fossati, Giovanna Tosi, Roberto S. Accolla, Laura Borsi

Research output: Contribution to journalArticlepeer-review


Treatment of tumor-bearing mice with mouse (m)TNF-α, targeted to tumor vasculature by the anti-ED-B fibronectin domain antibody L19(scFv) and combined with melphalan, induces a therapeutic immune response. Upon treatment, a highly efficient priming of CD4 + T cells and consequent activation and maturation of CD8 + CTL effectors is generated, as demonstrated by in vivo depletion and adoptive cell transfer experiments. Immunohistochemical analysis of the tumor tissue demonstrated massive infiltration of CD4 + and CD8 + T cells 6 days after treatment and much earlier in the anamnestic response to tumor challenge in cured mice. In fact, the curative treatment with L19mTNF-α and melphalan resulted in long-lasting antitumor immune memory, accompanied by a mixed Th1/Th2-type response and significant in vitro tumor-specific cytolytic activity. Finally, the combined treatment reduced the percentage and absolute number of CD4 +CD25 + regulatory T cells in the tumor-draining lymph nodes of mice responding to therapy, and this was associated with the establishment of protective immunity. These findings pave the way for alternative therapeutic strategies based on the targeted delivery of biological and pharmacological cytotoxic compounds that not only kill most of the tumor cells but, more importantly, trigger an effective and long-lasting antitumor adaptive immune response.

Original languageEnglish
Pages (from-to)3381-3392
Number of pages12
JournalEuropean Journal of Immunology
Issue number12
Publication statusPublished - Dec 2007


  • Antitumor immunity
  • CD4 priming
  • Melphalan
  • Th1/Th2 cells
  • TNF-α

ASJC Scopus subject areas

  • Immunology


Dive into the research topics of 'Therapy-induced antitumor vaccination by targeting tumor necrosis factor-α to tumor vessels in combination with melphalan'. Together they form a unique fingerprint.

Cite this