抗CD3抗体添加rIL-2誘導LAK細胞の抗腫瘍活性に関する研究
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This study investigated two different culture systems used to obtain effective lymphokine activated killer (LAK) cells for adoptive immunotherapy (AIT). These LAK cells Were induced from peripheral blood mononuclear cells derived from early (stage I and II: UICC) and advanced stage (stage III and IV: UICC) head and neck cancer patients and compared with cells derived from healthy volunteers which served as control.<BR>One culture system utilized only recombinant interleukin-2 (rIL-2 system). The other culture system utilized rIL-2 with anti-CD3 monoclonal antibody (rIL-2+ aCD3moAb system). Induction of LAK cells was evaluated by measuring proliferation, cytotoxicity (NK and LAK activity) and cell surface phenotypes at various culture periods (0, 2, 3, 5, 7, 10 and 14 days) in the two different systems.<BR>The rIL-2+ αCD3moAb system induced an approximately 10-fold increase in cell number compared to the rIL-2 system. Although there was no statistically significant difference, the number of LAK cells derived from cancer patients (early and advanced stage) was less than that derived from healthy volunteers in both culture systems.<BR>Of the culture periods evaluated, 5 to 7 days provided the highest level of LAK cell cytotoxicity in the rIL-2 system while 3 to 5 days yielded the highest cytotoxicity in the rIL-2 +αCD3mAb system.<BR>In addition, maximum cytotoxicity (NK and LAK activity) of LAK cells dervied from cancer patients (early and advanced stage) was delayed for 2 days compared with that of LAK cells derived from healthy volunteers. Although LAK cells from early and advanced stage cancer patients showed a similar time delay in reaching maximum cytotoxicity, the degree of cytotoxicity was lower in the advanced stage patients.<BR>LAK cells induced by the rIL-2αCD3moAb system showed a decrease in cytotoxicity compared with those induced by the rIL-2 system. However, the rIL-2 αCD3moAb system induced higher total cytotoxicity % cytotoxicity ×number of LAK cells, than the other system.<BR>After elimination of CD8+ cells from LAK cells induced by the each system, cytotoxicity (NK and LAK activity) increased in the rIL-2 +αCD3moAb system, but decreased in the rIL-2 system. Therefore, the functions of the CD<SUP>8+</SUP> cells induced by these two distinct culture systems were suggested to be different.<BR>These results suggest that AIT using LAK cells should be indicated in the treatment of early-stage cancer patients.
- 社団法人 日本口腔外科学会の論文
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- 抗CD3抗体添加rIL-2誘導LAK細胞の抗腫瘍活性に関する研究