Ferrini S, Cambiaggi A, Cantoni C, Canevari S, Mezzanzanica D, Colnaghi M I, Moretta L
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Int J Cancer Suppl. 1992;7:15-8.
MAbs directed against triggering surface molecules expressed by T lymphocytes (CD3, TCR, CD2, CD28) or by NK cells (CD2, CD16) are able to induce the functional program of these cells. These MAbs represent suitable reagents to construct biMAbs directed against TAA, in order to specifically target effector lymphocytes against tumor cells. Anti-CD3/anti-EGF-R biMAbs were constructed to specifically direct T lymphocytes against EGF-R+ tumor cells. Such biMAb are able to induce cytolysis of EGF-R+ tumor cell lines (A431, IGROV, KATO-III and U-87) by cytolytic CD3+ effector lymphocytes while tumor cells having low or absent expression of EGF-R were not lysed. In addition, both cytolytic T (CD8+) cells and non-cytolytic (CD4+) IL-2-expanded lymphocytes were able to secrete lymphokines upon contact with EGF-R+ tumor cells. To target NK cells against NK resistant ovarian carcinomas, we used an anti-CD16 Mab (IgG1) together with an anti-ovarian carcinoma MAb (IgG2a), to construct biMAbs using the hybrid hybridoma technique. The hybrid IgG1/IgG2a biMAb triggered the specific lysis of relevant target cells by resting NK cells and by a subset of NK clones. In addition, some TCR gamma/delta+ clones but not TCR alpha/beta+ clones could be targeted by the biMAb.
针对T淋巴细胞（CD3、TCR、CD2、CD28）或NK细胞（CD2、CD16）表达的触发表面分子的单克隆抗体能够诱导这些细胞的功能程序。这些单克隆抗体是构建针对肿瘤相关抗原（TAA）的双特异性抗体的合适试剂，以便将效应淋巴细胞特异性地靶向肿瘤细胞。构建了抗CD3/抗表皮生长因子受体（EGF-R）双特异性抗体，以将T淋巴细胞特异性地导向EGF-R阳性肿瘤细胞。这种双特异性抗体能够通过细胞毒性CD3+效应淋巴细胞诱导EGF-R阳性肿瘤细胞系（A431、IGROV、KATO-III和U-87）的细胞溶解，而EGF-R表达低或无表达的肿瘤细胞则不被溶解。此外，细胞毒性T（CD8+）细胞和非细胞毒性（CD4+）白细胞介素-2扩增淋巴细胞在与EGF-R阳性肿瘤细胞接触时都能够分泌淋巴因子。为了将NK细胞靶向对NK有抗性的卵巢癌，我们使用抗CD16单克隆抗体（IgG1）和抗卵巢癌单克隆抗体（IgG2a），利用杂交杂交瘤技术构建双特异性抗体。杂交IgG1/IgG2a双特异性抗体触发了静息NK细胞和一部分NK克隆对相关靶细胞的特异性溶解。此外，一些TCRγ/δ+克隆而不是TCRα/β+克隆可以被双特异性抗体靶向。
