CD4⁺ T lymphocytes play an important role in controlling many malignancies. The modulation of CD4⁺ T cells through immunomodulatory or cytotoxic drugs could change the course of disease progression for disorders such as autoimmunity, immunodeficiency, and cancer. Here, we demonstrate that anti-CD4 conjugated polymeric nanogels can deliver a small molecule cargo to primary CD4⁺ T cells and a CD4^high T cell lymphoma. The antibody conjugation not only increased the uptake efficiency of the nanogel (NG) by CD4⁺ T cells but also decreased the non-specific uptake of the NG by CD4^– lymphocytes. For T lymphoma cell lines, the mertansine-loaded conjugate displayed a dose-dependent cell growth inhibition at 17 ng/mL antibody concentration. On the other hand, antibody-drug conjugate (ADC)-type formulation of the anti-CD4 reached similar levels of cell growth inhibition only at the significantly higher concentration of 1.8 μg/mL. NG and antibody conjugates have the advantage of carrying a large payload to a defined target in a more efficient manner as it needs far less antibody to achieve a similar outcome.

中文翻译：

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靶向CD4 +细胞与抗CD4结合的巯基丙氨酸负载的纳米凝胶。

CD4 ⁺ T淋巴细胞在控制许多恶性肿瘤中起着重要作用。通过免疫调节或细胞毒性药物对CD4 ⁺ T细胞的调节可改变自身免疫，免疫缺陷和癌症等疾病的疾病进程。在这里，我们证明了抗CD4偶联的聚合物纳米凝胶可以将小分子货物递送至原代CD4 ⁺ T细胞和CD4^高T细胞淋巴瘤。抗体结合不仅增加了CD4 ⁺ T细胞对纳米凝胶（NG）的吸收效率，而且降低了CD4 ⁺对NG的非特异性吸收^–淋巴细胞。对于T淋巴瘤细胞系，负载丹参素的结合物在17 ng / mL抗体浓度下表现出剂量依赖性的细胞生长抑制作用。另一方面，抗CD4的抗体-药物偶联物（ADC）型制剂只有在明显更高的1.8μg/ mL浓度下才能达到相似的细胞生长抑制水平。NG和抗体偶联物的优势在于，它可以以更有效的方式将较大的有效载荷运送到定义的靶标，因为它只需很少的抗体即可获得相似的结果。