Optimal timing for the collection and in vitro expansion of cytotoxic CD56(+) lymphocytes from patients undergoing autologous peripheral blood stem cell transplantation

To identify the optimal time for the collection of CD56(+) cytotoxic lympho cytes for adoptive immunotherapy in patients undergoing high-dose chemother apy (HDCT) and peripheral blood stem cell (PBSC) transplantation, 18 breast cancer patients receiving either three cycles of epirubicin/paclitaxel (CT x 3) followed by HDCT and PBSC transplantation (n = 12) or CTx6 (n = 6) we re studied. Blood samples were obtained before each CT/HDCT cycle, from PBS C collections, and repeatedly after autografting for up to 12 months. The n umber of CD56(+)3(-) and CD56(+)3(-) lymphocytes, their in vitro expandabil ity with interleukin-2, and their cytotoxicity against MCF-7 and Daudi cell s were analyzed. Six healthy females served as controls. CD56(+) cell count s in both treatment groups were subnormal but stable during the observation period. The cytotoxicity of the expanded CD56(+) cells was normal and unaf fected by the treatment. The in vitro CD56(+) cell expandability (controls, 100 +/- 31-fold, mean +/- SEM) was normal before CT1 and CT2, but reduced in PBSC harvests performed after CT2 and application of G-CSF (21 +/- 6-fol d; p < 0.01). After PBSC harvesting, the CD56(+) cell expandability increas ed to 185 +/- 74-fold and 170 +/- 69-fold (before CT3 and HDCT). This incre ase was not observed in those patients who did not undergo PBSC mobilizatio n. Two weeks after autografting, the CD56(+) cell expandability was minimal (6 +/- 1-fold), and recovered to 34 +/- 6-fold. Thus, CT, HDCT and autogra fting do not alter the frequency and inducible cytotoxicity of CD56(+) cell s in breast cancer patients. However, the proliferative capacity of CD56(+) cells obtained from PBSC harvests and after autografting is impaired. Ther efore, instead of the PBSC graft, maximally expandable CD56(+) cells obtain ed at least 1 week after PBSC collection should be considered for adoptive immunotherapy after PBSC autografting.