Abstract

We have previously established the suitability of dendritic cells that have endocytosed apoptotic B-CLL cells (Apo-DC) as an antigen presentation platform to stimulate autologous antileukemic immune responses. The safety as well as immunological and clinical efficacy of Apo-DC vaccination was tested in a phase I/II clinical trial. CLL patients (Rai stage 0–2) who did not require concurrent therapy were leukapheresed and CD14+ monocytes as well as CD19+ B-CLL cells were purified immunomagnetically. Dendritic cells were generated ex vivo with GM-CSF and IL-4. Apoptotic bodies were obtained by irradiating B-CLL cells and overnight culture. DC were allowed to endocytose the apoptotic bodies and further matured with TNFα. The first cohort of 5 patients received 4 doses of the vaccine 2 weeks apart and a 5th dose at week 14. Each vaccine dose comprised of 107 autologous Apo-DC. The second cohort of 5 patients received the vaccine in a similar schedule with the addition of 75 μg of GM-CSF (Leukine™, Berlex Laboratories, Richmond VA) with every vaccine administration. Patients are scheduled to be monitored for a minimum of 52 weeks which has been completed for all of the patients in cohort 1 and is ongoing for cohort 2 The vaccine was well tolerated and occasional, low-grade toxicity was associated with the administration of GM-CSF. 4/5 patients in cohort 1 and 3/5 patients in cohort 2 responded immunologically in terms of increase in T cell proliferation or γ-IFN ELISPOT against autologous leukemic targets compared to prevaccination levels. Analysis of T cell responses at week 8 and week 16 following vaccination did not demonstrate an obvious augmentation of immunity by GM-CSF. One patient in cohort 1 demonstrated a transient decrease in WBC counts but no significant clinical responses have been noted thus far. Our results demonstrate that it is feasible to enrich monocyte precursors and generate Apo-DC for vaccinating patients with high count B-CLL. No significant toxicity was associated with this approach to vaccination therapy. The clinical efficacy of Apo-DC vaccination in CLL remains to be determined at the termination of the clinical trial.

Author notes

Disclosure: No relevant conflicts of interest to declare.