Purpose: This study was aimed at evaluating the feasibility, safety, immunological and clinical responses in patients with Follicular lymphoma (FL) treated with monocyte-derived dendritic cells generated in the presence of interferon-alpha and GM-CSF (IFN-DC) in combination with low doses of Rituximab (R). Experimental Design: Firstly, we analyzed in vitro and in vivo the immunological properties of IFN-DC against FL. Thus, we performed a phase I trial in 8 refractory and relapsed FL patients based on sequential intranodal injections of low-dose of R and unloaded IFN-DC and report the safety, clinical and immunological results of the enrolled patients. Results: Preclinical studies indicated that IFN-DC can synergize with R leading to increased cytotoxicity and T cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37% and remission is still ongoing in 2/4 of responding patients (median followup 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T cell responses by CD107 degranulation or IFN- ELISPOT assay against patient-specific tumor IGHV sequences. Conclusions: These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in cancer patients.

Clinical and antitumor immune responses In Relapsed/Refractory Follicular Lymphoma patients after intranodal injections of IFNα-Dendritic Cells and Rituximab / Cox, Maria Christina; Castiello, Luciano; Mattei, Mauro; Santodonato, Laura; D'Agostino, Giuseppina; Muraro, Elena; Martorelli, Debora; Lapenta, Caterina; Di Napoli, Arianna; Di Landro, Francesca; Cangemi, Michela; Pavan, Antonio; Castaldo, Paolo; Hohaus, Stefan; Donati, Simona; Montefiore, Enrica; Berdini, Cinzia; Carlei, Davide; Monque, Domenica M; Ruco, Luigi; Prosperi, Daniela; Tafuri, Agostino; Spadaro, Francesca; Sestili, Paola; Spada, Massimo; Dolcetti, Riccardo; Santini, Stefano Maria; Rozera, Carmela; Aricò, Eleonora; Capone, Imerio; Belardelli, Filippo. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - Jun 6(2019), pp. 1-34. [10.1158/1078-0432.CCR-19-0709]

Clinical and antitumor immune responses In Relapsed/Refractory Follicular Lymphoma patients after intranodal injections of IFNα-Dendritic Cells and Rituximab

Di Napoli, Arianna;Pavan, Antonio;BERDINI, CINZIA;Ruco, Luigi;Prosperi, Daniela;Tafuri, Agostino;
2019

Abstract

Purpose: This study was aimed at evaluating the feasibility, safety, immunological and clinical responses in patients with Follicular lymphoma (FL) treated with monocyte-derived dendritic cells generated in the presence of interferon-alpha and GM-CSF (IFN-DC) in combination with low doses of Rituximab (R). Experimental Design: Firstly, we analyzed in vitro and in vivo the immunological properties of IFN-DC against FL. Thus, we performed a phase I trial in 8 refractory and relapsed FL patients based on sequential intranodal injections of low-dose of R and unloaded IFN-DC and report the safety, clinical and immunological results of the enrolled patients. Results: Preclinical studies indicated that IFN-DC can synergize with R leading to increased cytotoxicity and T cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37% and remission is still ongoing in 2/4 of responding patients (median followup 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T cell responses by CD107 degranulation or IFN- ELISPOT assay against patient-specific tumor IGHV sequences. Conclusions: These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in cancer patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1280920
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