Fig. 2.

Possible schedules for the clinical exploitation of IFN-DC in the treatment of follicular lymphoma. Enrolled patients undergo leukapheresis to collect PBMC and purify blood monocytes necessary for IFN-DC generation. Large numbers of partially-mature IFN-DC can be easily obtained at one time point from purified peripheral blood monocytes cultured in the presence IFN-α and GM-CSF, loaded or not with tumor antigens, and cryopreserved in ready-for-use aliquots for the programmed cycles of treatment. On the right is depicted the prototypical schedule of intranodal therapy already performed in the phase I trial in 8 patients with refractory and relapsed FL. It is mainly based on sequential in situ injections of low-dose of rituximab and unloaded IFN-DC. Rituximab administration is followed, 24 h later, by the injection of unloaded IFN-DC. The main criteria for eligibility include biopsy-confirmed indolent CD20 + follicular lymphoma, low tumor burden and superficial accessible lesions. The intranodal injections are guided by ultrasound and performed by a radiologist to ensure correct administration. The treatment cycle is repeated at two-week intervals, possibly targeting a different accessible lymphoma lesion. According to the therapeutic vaccination strategy shown in the left side of the figure, IFN are loaded in vitro with autologous lymphoma antigens and are administered intradermally, in close vicinity to axillary and inguinal lymph nodes or directly administered into a healthy lymph node. The vaccination cycles are repeated at two-week intervals. Conceivably, IFN-DC-based monotherapy can evolve in chemotherapy-free combinatorial therapy regimens with immune checkpoint inhibiting antibodies, agonistic antibodies or immunomodulating drugs