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Biological Character of RetroNectin Activated Cytokine-Induced Killer Cells.

Han L, Shang YM, Song YP, Gao QL - J Immunol Res (2016)

Bottom Line: Median survival time (mOS) after first R-CIK cell infusion was 10.57 months; the 1-year survival rate was 38.5%.No serious toxicity was associated with R-CIK cell infusion.In conclusion, RetroNectin may enhance antitumor activity of CIK cells: it is safe for use in treating pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan 450008, China.

ABSTRACT
Adoptive cell therapy (ACT) using autologous cytokine-induced killer (CIK) cells is a promising treatment for metastatic carcinomas. In this study, we investigated the impact of RetroNectin on the proliferation, phenotype alternation, cytokine secretion, and cytotoxic activity of CIK cells from pancreatic cancer patients. Furthermore, we treated 13 patients with metastatic or locally advanced pancreatic cancer using autologous RetroNectin-activated CIK cells (R-CIK cells) alone or in combination with chemotherapy. Compared with only CD3 activated CIK cells (OKT-CIK cells), R-CIK cells showed stronger and faster proliferative ability, with a lower ratio of spontaneous apoptosis. Moreover, this ability continued after IL-2 was withdrawn from the culture system. R-CIK cells could also secrete higher levels of IL-2 and lower levels of IL-4 and IL-5 versus OKT-CIK cells. There was no difference between OKT-CIK and R-CIK cells in cytotoxic ability against lymphoma cell line K562. In patients who received auto-R-CIK cell infusion therapy, the overall objective response rate was 23.1%. Median survival time (mOS) after first R-CIK cell infusion was 10.57 months; the 1-year survival rate was 38.5%. No serious toxicity was associated with R-CIK cell infusion. In conclusion, RetroNectin may enhance antitumor activity of CIK cells: it is safe for use in treating pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus

RetroNectin activated CIK cells had stronger proliferative ability. (a) Proliferative curve of OKT-CIK and R-CIK cells. The proliferative speed of R-CIK cells was much higher than that of OKT-CIK cells, n = 5. (b) Mean percentage of OKT-CIK and R-CIK cells undergoing early apoptosis (Annexin+PI−) and late apoptosis/necrosis (Annexin+PI+). ∗P < 0.05 for the comparison, n = 5. (c) Continual proliferative curve of OKT-CIK and R-CIK cells in medium without IL-2. R-CIK cells could continue expanding 4 days after IL-2 was withdrawn from the medium, and the maximum average amplification is 6 times. OKT-CIK cells could only continue expanding 2 days in the same condition, and the maximum average amplification is 3 times, n = 5. (d) Shape of cultured OKT-CIK and R-CIK cells (400x).
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fig1: RetroNectin activated CIK cells had stronger proliferative ability. (a) Proliferative curve of OKT-CIK and R-CIK cells. The proliferative speed of R-CIK cells was much higher than that of OKT-CIK cells, n = 5. (b) Mean percentage of OKT-CIK and R-CIK cells undergoing early apoptosis (Annexin+PI−) and late apoptosis/necrosis (Annexin+PI+). ∗P < 0.05 for the comparison, n = 5. (c) Continual proliferative curve of OKT-CIK and R-CIK cells in medium without IL-2. R-CIK cells could continue expanding 4 days after IL-2 was withdrawn from the medium, and the maximum average amplification is 6 times. OKT-CIK cells could only continue expanding 2 days in the same condition, and the maximum average amplification is 3 times, n = 5. (d) Shape of cultured OKT-CIK and R-CIK cells (400x).

Mentions: Three days after activation by OKT3 alone or OKT3 combined with RetroNectin, both OKT-CIK and R-CIK cells began a logarithmic growth stage, but the growth speed of R-CIK cells was much higher than that of OKT-CIK cells (Figure 1(a)). Both OKT-CIK and R-CIK cells achieved growth platform after 15 days in culture: the OKT-CIK cells displayed 100 times amplification at this time, while the R-CIK cells displayed 200 times amplification (Figure 1(a)). Coincident with the growth speed, the spontaneous apoptosis of R-CIK cells was lower than that of OKT-CIK cells (Figure 1(b)). After IL-2 was withdrawn from the medium, R-CIK cells could continue growing to 6 times amplification, while OKT-CIK cells could only grow to 3 times amplification (Figure 1(c)). These results indicate that R-CIK cells activated by RetroNectin have much stronger proliferative ability than only CD3 activated CIK cells. There were also some shape differences between OKT-CIK and R-CIK cells; OKT-CIK cells displayed easily formed cells aggregates, while R-CIK cells displayed dispersed growth (Figure 1(d)).


Biological Character of RetroNectin Activated Cytokine-Induced Killer Cells.

Han L, Shang YM, Song YP, Gao QL - J Immunol Res (2016)

RetroNectin activated CIK cells had stronger proliferative ability. (a) Proliferative curve of OKT-CIK and R-CIK cells. The proliferative speed of R-CIK cells was much higher than that of OKT-CIK cells, n = 5. (b) Mean percentage of OKT-CIK and R-CIK cells undergoing early apoptosis (Annexin+PI−) and late apoptosis/necrosis (Annexin+PI+). ∗P < 0.05 for the comparison, n = 5. (c) Continual proliferative curve of OKT-CIK and R-CIK cells in medium without IL-2. R-CIK cells could continue expanding 4 days after IL-2 was withdrawn from the medium, and the maximum average amplification is 6 times. OKT-CIK cells could only continue expanding 2 days in the same condition, and the maximum average amplification is 3 times, n = 5. (d) Shape of cultured OKT-CIK and R-CIK cells (400x).
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Related In: Results  -  Collection

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fig1: RetroNectin activated CIK cells had stronger proliferative ability. (a) Proliferative curve of OKT-CIK and R-CIK cells. The proliferative speed of R-CIK cells was much higher than that of OKT-CIK cells, n = 5. (b) Mean percentage of OKT-CIK and R-CIK cells undergoing early apoptosis (Annexin+PI−) and late apoptosis/necrosis (Annexin+PI+). ∗P < 0.05 for the comparison, n = 5. (c) Continual proliferative curve of OKT-CIK and R-CIK cells in medium without IL-2. R-CIK cells could continue expanding 4 days after IL-2 was withdrawn from the medium, and the maximum average amplification is 6 times. OKT-CIK cells could only continue expanding 2 days in the same condition, and the maximum average amplification is 3 times, n = 5. (d) Shape of cultured OKT-CIK and R-CIK cells (400x).
Mentions: Three days after activation by OKT3 alone or OKT3 combined with RetroNectin, both OKT-CIK and R-CIK cells began a logarithmic growth stage, but the growth speed of R-CIK cells was much higher than that of OKT-CIK cells (Figure 1(a)). Both OKT-CIK and R-CIK cells achieved growth platform after 15 days in culture: the OKT-CIK cells displayed 100 times amplification at this time, while the R-CIK cells displayed 200 times amplification (Figure 1(a)). Coincident with the growth speed, the spontaneous apoptosis of R-CIK cells was lower than that of OKT-CIK cells (Figure 1(b)). After IL-2 was withdrawn from the medium, R-CIK cells could continue growing to 6 times amplification, while OKT-CIK cells could only grow to 3 times amplification (Figure 1(c)). These results indicate that R-CIK cells activated by RetroNectin have much stronger proliferative ability than only CD3 activated CIK cells. There were also some shape differences between OKT-CIK and R-CIK cells; OKT-CIK cells displayed easily formed cells aggregates, while R-CIK cells displayed dispersed growth (Figure 1(d)).

Bottom Line: Median survival time (mOS) after first R-CIK cell infusion was 10.57 months; the 1-year survival rate was 38.5%.No serious toxicity was associated with R-CIK cell infusion.In conclusion, RetroNectin may enhance antitumor activity of CIK cells: it is safe for use in treating pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan 450008, China.

ABSTRACT
Adoptive cell therapy (ACT) using autologous cytokine-induced killer (CIK) cells is a promising treatment for metastatic carcinomas. In this study, we investigated the impact of RetroNectin on the proliferation, phenotype alternation, cytokine secretion, and cytotoxic activity of CIK cells from pancreatic cancer patients. Furthermore, we treated 13 patients with metastatic or locally advanced pancreatic cancer using autologous RetroNectin-activated CIK cells (R-CIK cells) alone or in combination with chemotherapy. Compared with only CD3 activated CIK cells (OKT-CIK cells), R-CIK cells showed stronger and faster proliferative ability, with a lower ratio of spontaneous apoptosis. Moreover, this ability continued after IL-2 was withdrawn from the culture system. R-CIK cells could also secrete higher levels of IL-2 and lower levels of IL-4 and IL-5 versus OKT-CIK cells. There was no difference between OKT-CIK and R-CIK cells in cytotoxic ability against lymphoma cell line K562. In patients who received auto-R-CIK cell infusion therapy, the overall objective response rate was 23.1%. Median survival time (mOS) after first R-CIK cell infusion was 10.57 months; the 1-year survival rate was 38.5%. No serious toxicity was associated with R-CIK cell infusion. In conclusion, RetroNectin may enhance antitumor activity of CIK cells: it is safe for use in treating pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus