Clinical study of LAK adoptive immunotherapy for angiosarcoma enhanced by anti-angiosarcoma × anti-CD3 bispecific antibody

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LAK adoptive immunotherapy is effective in the treatment of angiosarcoma. To enhance the effect of this immunotherapy, we devised the utility of a bispecific antibody (BSAb) to crosslink between tumor cells and LAK cells. We established an anti-angiosarcoma specific monoclonal antibody HEW-3 using a human angiosarcoma cell line ISO-HAS as an immunogen (Int. J. Cancer 81 : 305-308, 1999). HEW-3 was an IgM antibody and recognizes a 43 Kd molecule in the immunogen. The BSAb was made from the respective F(ab') _2 regions of HEW-3 for angiosarcoma cell and anti-CD3 antibody for LAK cell. The BSAb enhanced LAK cytotoxicity against ISO-HAS cells in a dose- and time-dependent manner. Moreover, the cytotoxic activity was related to a dose of TNFα measured in the supernates in vitro. The in vivo effect of the BSAb in LAK immunotherapy was studied in a human angiosarcoma SCID mouse model (WB-SCID) established by us (J. Dermatol. Sci. 27 : 88-94, 2001). The growing angiosarcoma was suppressed significantly only by initial 4-times intra-lesional injection of the BSAb immunotherapy in comparison with LAK immunotherapy alone. Based on these basic results, we treated three patients with angiosarcoma by this therapy. The 2.5μg BSAb combined with LAK cells was administered to two patients with angiosarcoma of the scalp by intra-lesional injection, and the 15 μg BSAb combined with LAK cells to one patient with intracranial angiosarcoma by selective intra-arterial injection. The increase in the human anti-mouse antibody prevented continuous administration, but we detected the clinical exact but temporal effect of this immunotherapy in each patient. Side effects in this immunotherapy were only fever in one patient and CRP elevation in two patients without visceral damage. This prospective study could promote the making of human-type BSAb for LAK immunotherapy of angiosarcoma in the near future.