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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Research

Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma

Authors: Carmela Rozera, Giancarlo Antonini Cappellini, Giuseppina D’Agostino, Laura Santodonato, Luciano Castiello, Francesca Urbani, Iole Macchia, Eleonora Aricò, Ida Casorelli, Paola Sestili, Enrica Montefiore, Domenica Monque, Davide Carlei, Mariarosaria Napolitano, Paola Rizza, Federica Moschella, Carla Buccione, Roberto Belli, Enrico Proietti, Antonio Pavan, Paolo Marchetti, Filippo Belardelli, Imerio Capone

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

Background

Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies have resulted in a marked antitumor effect, but most responses are partial and some degree of toxicity remain the major concerns.
Dendritic cells play a key role in the activation of the immune system and have been typically used as ex vivo antigen-loaded cell drugs for cancer immunotherapy.
Another approach consists in intratumoral injection of unloaded DCs that can exploit the uptake of a wider array of tumor-specific and individual unique antigens. However, intratumoral immunization requires DCs endowed at the same time with properties typically belonging to both immature and mature DCs (i.e. antigen uptake and T cell priming). DCs generated in presence of interferon-alpha (IFN-DCs), due to their features of partially mature DCs, capable of efficiently up-taking, processing and cross-presenting antigens to T cells, could successfully carry out this task. Combining intratumoral immunization with tumor-destructing therapies can induce antigen release in situ, facilitating the injected DCs in triggering an antitumor immune response.

Methods

We tested in a phase I clinical study in advanced melanoma a chemo-immunotherapy approach based on unloaded IFN-DCs injected intratumorally one day after administration of dacarbazine. Primary endpoint of the study was treatment safety and tolerability. Secondary endpoints were immune and clinical responses of patients.

Results

Six patients were enrolled, and only three completed the treatment. The chemo-immunotherapy was well tolerated with no major side effects. Three patients showed temporary disease stabilization and two of them showed induction of T cells specific for tyrosinase, NY-ESO-1 and gp100. Of interest, one patient showing a remarkable long-term disease stabilization kept showing presence of tyrosinase specific T cells in PBMC and high infiltration of memory T cells in the tumor lesion at 21 months.

Conclusion

We tested a chemo-immunotherapeutic approach based on IFN-DCs injected intratumorally one day after DTIC in advanced melanoma. The treatment was well tolerated, and clinical and immunological responses, including development of vitiligo, were observed, therefore warranting additional clinical studies aimed at evaluating efficacy of this approach.

Trial registration

Trial Registration Number not publicly available due to EudraCT regulations: https://​www.​clinicaltrialsre​gister.​eu/​doc/​EU_​CTR_​FAQ.​pdf
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Metadata
Title
Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma
Authors
Carmela Rozera
Giancarlo Antonini Cappellini
Giuseppina D’Agostino
Laura Santodonato
Luciano Castiello
Francesca Urbani
Iole Macchia
Eleonora Aricò
Ida Casorelli
Paola Sestili
Enrica Montefiore
Domenica Monque
Davide Carlei
Mariarosaria Napolitano
Paola Rizza
Federica Moschella
Carla Buccione
Roberto Belli
Enrico Proietti
Antonio Pavan
Paolo Marchetti
Filippo Belardelli
Imerio Capone
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0473-5

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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