Cancer Immunology, Immunotherapy

, Volume 64, Issue 1, pp 113–121 | Cite as

Armed antibodies for cancer treatment: a promising tool in a changing era

  • Riccardo Danielli
  • Roberto Patuzzo
  • Pier Adelchi Ruffini
  • Andrea Maurichi
  • Leonardo Giovannoni
  • Giuliano Elia
  • Dario Neri
  • Mario Santinami
Focussed Research Review

Abstract

Advances in the understanding of tumor immunology and molecular biology of melanoma cells have favored a larger application of immunotherapy and targeted therapies in the clinic. Several selective mutant gene inhibitors and immunomodulating antibodies have been reported to improve overall survival or progression-free survival in metastatic melanoma patients. However, despite impressive initial responses, patients treated with selective inhibitors relapse quickly, and toxicities associated to the use of immunomodulating antibodies are not easily manageable. In this sense, the concept of using antibodies as delivery vehicles for the preferential in vivo localization of the drug at the site of disease with reduction of side effects has raised particular interest. Antibody–cytokine fusion proteins (termed immunocytokines) represent a new simple and effective way to deliver the immunomodulatory payload at the tumor site, with the aim of inducing both local and systemic antitumoral immune responses and limiting systemic toxicities. Several clinical trials have been conducted and are actually ongoing with different immunocytokines, in several tumor histotypes. In metastatic melanoma patients, different drug delivery modalities such as systemic, loco-regional and intratumoral are under investigation. In this review, the rationale for the use of L19-IL2 and L19-TNF, two clinical stage immunocytokines produced by the Philogen group, as well as opportunities for their future development will be discussed.

Keywords

NIBIT 2013 Immunocytokines Intralesional immunotherapy Armed antibodies 

Abbreviations

AEs

Adverse events

b.w.

Body weight

CR

Complete responses

CTLA-4

Cytotoxic T-lymphocyte antigen 4

DCR

Disease control rate

EDB

Extra-domain B

IgG

Immunoglobulin G

IIT

Intralesional immunotherapy

IL2

Interleukin-2

IL4

Interleukin-4

IL12

Interleukin-12

ILP

Isolated limb perfusion

irRC

Immune-related response criteria

NK

Natural killer

OS

Overall survival

PD1

Programmed cell death protein 1

PET

Positron Emission Tomography

PFS

Progression-free survival

PR

Partial response

RECIST

Response criteria in solid tumors

TNF

Tumor necrosis factor α

WHO

World Health Organization

wt

Wild-type

Notes

Acknowledgments

Dario Neri acknowledges funding from ETH Zürich and the Swiss National Science Foundation.

Conflict of interest

Riccardo Danielli is a consultant/advisory board member for Philogen S.p.A. Roberto Patuzzo, Andrea Maurichi and Mario Santinami took part in the clinical trial sponsored by Philogen: “A phase II study of intratumoral application of L19-IL2/L19-TNF in melanoma patients in clinical stage III or stage IV M1a with the presence of injectable cutaneous and/or subcutaneous lesions.” Pier Adelchi Ruffini is an employee of Dompé S.p.A., a minority shareholder of Philogen S.p.A. Leonardo Giovannoni and Giuliano Elia are employees of Philogen S.p.A. Dario Neri is co-founder, shareholder and Board Member of Philogen S.p.A.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Riccardo Danielli
    • 1
  • Roberto Patuzzo
    • 2
  • Pier Adelchi Ruffini
    • 3
  • Andrea Maurichi
    • 2
  • Leonardo Giovannoni
    • 4
  • Giuliano Elia
    • 4
  • Dario Neri
    • 5
  • Mario Santinami
    • 2
  1. 1.Medical Oncology and Immunotherapy, Azienda Ospedaliera Universitaria Senese, Istituto Toscano TumoriUniversity Hospital of SienaSienaItaly
  2. 2.Department of Surgery, Melanoma and Sarcoma UnitFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
  3. 3.Dompé S.p.A.MilanItaly
  4. 4.Philogen S.p.A.SienaItaly
  5. 5.Department of Chemistry and Applied BiosciencesETH ZürichZurichSwitzerland

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