[Autologous CIK cell infusion promotes amplification ability of CD3⁺ CD56⁺ cells when re-preparation from patients with malignant tumors].

OBJECTIVE: To investigate the effects of the autologous cytokine-induced killer (CIK) cell infusion on the subpopulation distribution and activity of the CIK cells from the patients with malignant tumors when prepared in the same liquid culture system again.

METHODS: A total of 201 patients who gave a written consent and received 2 courses of therapeutic infusion of CIK cells were divided into ≤ 90-day group in which the secondary preparation of CIK cells was performed in less than 90 days after the primary infusion and >90-day group in which the secondary preparation of CIK cells was performed in more than 90 days after the primary infusion. The proliferation and subtypes, including CD3⁺ cells, CD3⁺ CD4⁺ cells, CD3⁺ CD8⁺ cells, and CD3⁺ CD56⁺ cells, of CIK cells were analyzed by hemocytometer with trypan blue exclusion and flow cytometry, respectively. The expression of NKG2D receptor was also detected using flow cytometry. The cytotoxicity against K562 cells was analyzed using lactate dehydrogenase (LDH) release.

RESULTS: The percentage of CD3⁺ CD56⁺ cell subpopulation in the secondary preparation of CIK cells in ≤ 90-day group [(16.7 ± 9.1)%] was higher than that in the primary preparation of CIK cells [(13.5 ± 8.6)%] (P<0.01). Furthermore, the percentage of NKG2D in the secondary CIK cell preparation [(84.1 ± 10.8)%] was significantly higher than that in the primary CIK cell preparation [(81.1 ± 14.8)%] in ≤ 90-day group (P<0.05). In contrast, the percentage of CD3⁺ CD4⁺ cells in the secondary CIK cell preparation [(15.2 ± 9.7)%] was significantly lower than that in the primary CIK cell preparation [(17.6 ± 12.5)%] (P<0.01). However, no significant differences in CD3⁺ CD56⁺ cell subpopulation and expression of NKG2D was detected between the primary and secondary CIK cell preparation in >90 d group, although the percentage of CD3⁺ CD4⁺ cells in the secondary CIK cell preparation [(14.5 ± 9.4)%] was significantly lower than that in the primary CIK cell preparation [(18.2 ± 12.9)%] (P<0.01). In addition, no significant differences in total cell number and cytotoxic activity against K562 cells between the primary and secondary CIK cell preparation was detected either in >90-day group or in ≤ 90-day group.

CONCLUSION: CIK cell infusion can facilitate and enhance the proliferation and differentiation of the precursor cells of the CD3⁺ CD56⁺ subpopulation in the same CIK cell culture system and this effect does not last more than 90 days, suggesting that the secondary CIK cell infusion should be performed within 90 days in order to obtain the better therapeutic efficacy.