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

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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.

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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

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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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Authors and Affiliations

  1. Medical Oncology and Immunotherapy, Azienda Ospedaliera Universitaria Senese, Istituto Toscano Tumori, University Hospital of Siena, Strada delle Scotte, 53100, Siena, Italy

    Riccardo Danielli

  2. Department of Surgery, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Roberto Patuzzo, Andrea Maurichi & Mario Santinami

  3. Dompé S.p.A., Milan, Italy

    Pier Adelchi Ruffini

  4. Philogen S.p.A., Siena, Italy

    Leonardo Giovannoni & Giuliano Elia

  5. Department of Chemistry and Applied Biosciences, ETH Zürich, Zurich, Switzerland

    Dario Neri

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  1. Riccardo Danielli
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  2. Roberto Patuzzo
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  3. Pier Adelchi Ruffini
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  4. Andrea Maurichi
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  8. Mario Santinami
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Correspondence to Riccardo Danielli.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Eleventh Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, held in Siena, Italy, 17th- 19th October 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Danielli, R., Patuzzo, R., Ruffini, P.A. et al. Armed antibodies for cancer treatment: a promising tool in a changing era. Cancer Immunol Immunother 64, 113–121 (2015). https://doi.org/10.1007/s00262-014-1621-0

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