Induction of long-lasting antitumor immunity by concomitant cell therapy with allogeneic lymphocytes and trifunctional bispecific antibody

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• 作者：Shoshana Morecki ; Horst Lindhofer ; Elena Yacovlev ; Yael Gelf ; Peter Ruf ; Shimon Slavin
• 刊名：Experimental Hematology
• 出版年：2008
• 出版时间：August 2008
• 年：2008
• 卷：36
• 期：8
• 页码：997-1003
• 全文大小：268 K

文摘

Objective

Use of a trifunctional bispecific antibody (trAb) given concomitantly with allogeneic cell therapy to achieve an anti tumor effect without graft-vs-host disease (GVHD).

Materials and Methods

A trAb-directed against murine CD3 and human epithelial cell adhesion molecule (EpCAM) (BiLu), was given alone or concomitantly with interleukin (IL)-2–activated (LAK) H-2^b donor splenocytes to H-2^d/b mice inoculated with murine melanoma cells transfected with human EpCAM.

Results

A total of 32/38 mice treated with BiLu and LAK splenocytes, were tumor-free survivors without GVHD for >200 days following inoculation of a 100 % lethal tumor dose (5 × 10⁴). Of 28 disease-free surviving mice previously treated with LAK splenocytes and BiLu, 24 mice proved resistance to a second tumor challenge of 10⁴ cells given >210 days following the first tumor inoculation with no evidence of disease for >150 days. In contrast, only 4 of 13 disease-free survivor mice treated with naïve splenocytes and BiLu, and 5 of 10 disease-free survivor controls treated with BiLu only, resisted the second tumor challenge. Induction of antitumor immunity was more efficient and long-lasting (>150 days) in mice previously injected with a lethal tumor cell dose of 5 × 10⁴ cells than in mice previously inoculated with 5 × 10³ tumor cells.

Conclusion

Concomitantly treatment of allogeneic LAK cells and trAb-induced an efficient long-lasting antitumor immunity. Considering the documented efficacy of anti-EpCAM bispecific antibody in various metastatic cancers, clinical application of our approach may be justified in patients with minimal residual disease at high risk for tumor recurrence.