Azuma A, Yagita H, Okumura K, Kudoh S, Niitani H
4th Department of Internal Medicine, Nippon Medical School, Japan.
Cancer Immunol Immunother. 1994 May;38(5):294-8. doi: 10.1007/BF01525506.
Lymphokine-activated killer (LAK) cells exhibit a potent cytotoxicity to malignant cells in vitro. However, a satisfactory effect has not been obtained in many clinical studies except for a few cases. One of the most important reasons why cytolytic activity could not be exhibited in vivo is that LAK cells do not accumulate in the tumor tissue because of a lack of specificity. In the present study, we show the effect of a bispecific antibody (bsAb) on the accumulation of LAK cells around the small-cell lung carcinoma (SCLC) cell and the subsequent enhancement of LAK cell cytotoxicity against SCLC. When short-term(4 days)-cultured LAK cells were used, OKT3 x LU246 bsAb, which direct CD3+ T-LAK cells to the target cell, induced a similar level of cytotoxicity to that induced by 3G8 x LU246 bsAb, which directs CD16+ LAK cells. Long-term(21 days)-cultured LAK cells exhibited a reduced spontaneous cytotoxicity but retained high cytotoxic activity, which could be directed by OKT3 x LU246 or 3G8 x LU246 bsAb. The inhibitory effect of LAK cells on tumor cell clonogenicity in soft agar was also enhanced by both bsAb. These results indicate that application of the therapy with LAK cells and OKT3 x LU246 bsAb to SCLC patients might be a promising new method of adoptive immunotherapy.
淋巴因子激活的杀伤（LAK）细胞在体外对恶性细胞表现出强大的细胞毒性。然而，除少数病例外，许多临床研究并未取得令人满意的效果。体内无法表现出溶细胞活性的最重要原因之一是，由于缺乏特异性，LAK细胞不会在肿瘤组织中积聚。在本研究中，我们展示了双特异性抗体（bsAb）对小细胞肺癌（SCLC）细胞周围LAK细胞积聚的影响，以及随后LAK细胞对SCLC细胞毒性的增强。当使用短期（4天）培养的LAK细胞时，将CD3 + T-LAK细胞导向靶细胞的OKT3×LU246 bsAb诱导的细胞毒性水平与将CD16 + LAK细胞导向靶细胞的3G8×LU246 bsAb诱导的相似。长期（21天）培养的LAK细胞自发细胞毒性降低，但保留了高细胞毒性活性，这可由OKT3×LU246或3G8×LU246 bsAb引导。两种bsAb均增强了LAK细胞对软琼脂中肿瘤细胞克隆形成的抑制作用。这些结果表明，将LAK细胞和OKT3×LU246 bsAb疗法应用于SCLC患者可能是一种有前景的过继性免疫治疗新方法。
