Tobin Evan, Denardo Gerald, Zhang Nan, Epstein Alan L, Liu Cathy, Denardo Sally
Department of Internal Medicine, University of California, Davis, CA, USA.
Leuk Lymphoma. 2007 May;48(5):944-56. doi: 10.1080/10428190701272272.
Rituximab is effective in about one half of patients with indolent lymphoma. Even these patients relapse and develop rituximab resistance. To increase potency and circumvent resistance, the anti-lymphoma effects of rituximab, an anti-CD20 MAb(1), combined with chLym-1(2), an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC(3) and CDC(4). There were additive effects in all assays and synergism in cell lines, such as B35M, which displayed resistance to either MAb alone. In B35M cells, combined rituximab and chLym-1 induced a 27-fold direct reduction in viable cells, whereas equivalent concentrations of rituximab or chLym-1 alone induced only a 1-fold and 10-fold reduction in viable cells, respectively. Because these results occurred at MAb concentrations readily achievable in patients, they suggest that this combination immunotherapy regimen may increase the potency and range of effectiveness of these MAbs in lymphoma patients.
利妥昔单抗对约一半的惰性淋巴瘤患者有效。即便如此，这些患者仍会复发并产生利妥昔单抗耐药性。为了增强效力并规避耐药性，通过检测生长抑制、细胞死亡、凋亡诱导、抗体依赖的细胞介导的细胞毒性作用（ADCC）和补体依赖的细胞毒性作用（CDC），在人淋巴瘤细胞系中评估了抗CD20单克隆抗体（MAb）利妥昔单抗与抗HLA-DR单克隆抗体chLym-1联合使用时的抗淋巴瘤作用。在所有检测中均观察到了相加作用，在诸如B35M等对单一单克隆抗体均耐药的细胞系中还观察到了协同作用。在B35M细胞中，利妥昔单抗与chLym-1联合使用可使活细胞数量直接减少27倍，而同等浓度的利妥昔单抗或chLym-1单独使用时分别仅使活细胞数量减少1倍和10倍。鉴于这些结果是在患者易于达到的单克隆抗体浓度下出现的，故提示这种联合免疫治疗方案可能会增强这些单克隆抗体对淋巴瘤患者的效力和有效性范围。
