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

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).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.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 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 IFN-g ELISPOT assay against patient-specific tumor IGHV sequences.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

Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians

Background: Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Methods: Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Results: Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. Conclusions: At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices