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Dual-Targeting for the Elimination of Cancer Cells with Increased Selectivity

机译：双重目标消除具有更高选择性的癌细胞

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Here we review recombinant proteins with a capability for dual-targeting. These molecules address two different antigens on the same tumor cell and therefore are called “dual-targeting agents”. By virtue of binding a chosen pair of antigens on the malignant cell, preferential binding to antigen double-positive over single-positive cells can be achieved when both are present in the same environment. Therapeutic effects of such agents are based on different modes of action: (1) They can act as pro-apoptotic agents or by inhibiting pro-survival signals; (2) The dual recognition moiety can be fused to effector-domains, such as bacterial toxins or other drugs, leading to the generation of bispecific antibody-drug conjugates (ADCs); (3) Dual-targeting agents can further be used to redirect an effector-cell to the tumor. A new generation of scFv-derived fusion proteins are the tandem single chain triplebodies (sctbs), which carry two scFv binding sites for antigens on the tumor cell plus a third, specific for a trigger molecule on an effector cell. The ability of preferential or selective targeting of antigen double-positive over single-positive cells opens attractive new perspectives for the use of dual-targeting agents in cancer therapy, and possibly also for the treatment of certain inflammatory and autoimmune disorders.
机译：在这里，我们审查具有双重目标能力的重组蛋白。这些分子针对同一肿瘤细胞上的两种不同抗原，因此被称为“双重靶向剂”。通过将选择的一对抗原结合在恶性细胞上，当两者都存在于同一环境中时，可以实现与单阳性细胞的双阳性抗原优先结合。这些药物的治疗作用基于不同的作用方式：（1）它们可以作为促凋亡药物或通过抑制生存信号来发挥作用; （2）双重识别部分可以与效应域融合，例如细菌毒素或其他药物，从而导致双特异性抗体-药物缀合物（ADC）的产生; （3）双重靶向剂可进一步用于将效应细胞重定向至肿瘤。新一代的scFv衍生融合蛋白是串联单链三链体（sctbs），它在肿瘤细胞上带有两个抗原的scFv结合位点，另外一个对效应细胞上的触发分子具有特异性。相对于单阳性细胞，对双阳性抗原优先或选择性靶向的能力为在癌症治疗中使用双靶向剂，以及可能在某些炎症和自身免疫性疾病的治疗中打开了有吸引力的新观点。

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