Reali E, Guiliani A L, Spisani S, Moretti S, Gavioli R, Masucci G, Gambari R, Traniello S
Istituto di Chimica Biologica, Università degli Studi di Ferrara, Italy.
Clin Immunol Immunopathol. 1994 Apr;71(1):105-12. doi: 10.1006/clin.1994.1058.
17-1A is a murine monoclonal antibody (MAb) specific for the tumor-associated antigen CO17-1A on colorectal carcinoma cells. One of the tumor cell destruction mechanisms induced by in vivo immunotherapy with MAb17-1A has been claimed to be antibody-dependent cellular cytotoxicity (ADCC) by monocytes and NK cells. In the present study we investigated whether human neutrophils (PMN) could be involved in colorectal carcinoma cell lysis and whether IFN-gamma influences this function. We showed that neutrophils are capable of tumor lysis mediated by MAb17-1A, although to a lesser extent than are the mononuclear cells (PBMC). Neutrophil ADCC was, however, markedly increased in the presence of IFN-gamma. Enhancement by IFN-gamma was also observed for PBMC. ADCC by PMN required the binding of MAb17-1A to Fc gamma RIII (CD16) since anti-Fc gamma RIII MAbs efficiently blocked tumor cell lysis. In contrast, in the presence of IFN-gamma the neutralization of Fc gamma RIII did not affect MAb17-1A-mediated cytotoxicity, suggesting that receptors other than Fc gamma RIII were involved in the process. PBMC cytotoxicity was also inhibited by anti-CD16 antibodies but IFN-gamma did not overcome this effect. Finally, the scavenger enzymes superoxide dismutase and catalase did not block ADCC by PMN or PBMC, indicating that oxidants are not key factors in MAb17-1A-mediated lysis; however, in IFN-gamma-activated PMN the oxygen-dependent mechanism was in part involved in tumor lysis.
17-1A是一种鼠单克隆抗体（MAb），对结肠癌细胞上的肿瘤相关抗原CO17-1A具有特异性。用MAb17-1A进行体内免疫治疗诱导的肿瘤细胞破坏机制之一被认为是单核细胞和NK细胞介导的抗体依赖性细胞毒性（ADCC）。在本研究中，我们调查了人类中性粒细胞（PMN）是否参与结肠癌细胞的裂解，以及干扰素-γ是否影响该功能。我们发现中性粒细胞能够介导MAb17-1A诱导的肿瘤裂解，尽管程度低于单核细胞（PBMC）。然而，在干扰素-γ存在的情况下，中性粒细胞的ADCC显著增加。PBMC也观察到干扰素-γ的增强作用。PMN的ADCC需要MAb17-1A与FcγRIII（CD16）结合，因为抗FcγRIII单克隆抗体有效地阻断了肿瘤细胞裂解。相反，在干扰素-γ存在的情况下，FcγRIII的中和并不影响MAb17-1A介导的细胞毒性，这表明除FcγRIII之外的受体参与了该过程。抗CD16抗体也抑制了PBMC的细胞毒性，但干扰素-γ并未克服这种作用。最后，清除酶超氧化物歧化酶和过氧化氢酶并未阻断PMN或PBMC的ADCC，这表明氧化剂不是MAb17-1A介导的裂解中的关键因素；然而，在干扰素-γ激活的PMN中，氧依赖性机制部分参与了肿瘤裂解。
