Purpose: This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab. Patients and Methods: Firstly, we analyzed in vitro and in vivo the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients. Results: Preclinical studies indicated that IFN-DC can synergize with rituximab 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 follow-up 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ 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 patients with cancer.

Cox, M. C., Castiello, L., Mattei, M., Santodonato, L., D'Agostino, G., Muraro, E., Martorelli, D., Lapenta, C., Napoli, A. D., Landro, F. D., Cangemi, M., Pavan, A., Castaldo, P., Hohaus, S., Donati, S., Montefiore, E., Berdini, C., Carlei, D., Monque, D. M., Ruco, L., Prosperi, D., Tafuri, A., Spadaro, F., Sestili, P., Spada, M., Dolcetti, R., Santini, S. M., Rozera, C., Arico, E., Capone, I., Belardelli, F., Clinical and antitumor immune responses in relapsed/refractory follicular lymphoma patients after intranodal injections of IFNα-Dendritic cells and rituximab: A phase i clinical trial, <<CLINICAL CANCER RESEARCH>>, 2019; 25 (17): 5231-5241. [doi:10.1158/1078-0432.CCR-19-0709] [http://hdl.handle.net/10807/155742]

Clinical and antitumor immune responses in relapsed/refractory follicular lymphoma patients after intranodal injections of IFNα-Dendritic cells and rituximab: A phase i clinical trial

Hohaus, S.;
2019

Abstract

Purpose: This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab. Patients and Methods: Firstly, we analyzed in vitro and in vivo the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients. Results: Preclinical studies indicated that IFN-DC can synergize with rituximab 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 follow-up 26 months, range 11-47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ 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 patients with cancer.
Inglese
Cox, M. C., Castiello, L., Mattei, M., Santodonato, L., D'Agostino, G., Muraro, E., Martorelli, D., Lapenta, C., Napoli, A. D., Landro, F. D., Cangemi, M., Pavan, A., Castaldo, P., Hohaus, S., Donati, S., Montefiore, E., Berdini, C., Carlei, D., Monque, D. M., Ruco, L., Prosperi, D., Tafuri, A., Spadaro, F., Sestili, P., Spada, M., Dolcetti, R., Santini, S. M., Rozera, C., Arico, E., Capone, I., Belardelli, F., Clinical and antitumor immune responses in relapsed/refractory follicular lymphoma patients after intranodal injections of IFNα-Dendritic cells and rituximab: A phase i clinical trial, <<CLINICAL CANCER RESEARCH>>, 2019; 25 (17): 5231-5241. [doi:10.1158/1078-0432.CCR-19-0709] [http://hdl.handle.net/10807/155742]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/155742
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