Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 10003, United States.
Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 10003, United States.
Biomacromolecules. 2020 Jun 8;21(6):2473-2481. doi: 10.1021/acs.biomac.0c00442. Epub 2020 May 28.
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 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.
CD4 T 淋巴细胞在控制多种恶性肿瘤方面发挥着重要作用。通过免疫调节或细胞毒性药物来调节 CD4 T 细胞可以改变自身免疫、免疫缺陷和癌症等疾病的进展过程。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药物递送到原代 CD4 T 细胞和 CD4 T 细胞淋巴瘤中。抗体偶联不仅提高了 CD4 T 细胞对纳米凝胶(NG)的摄取效率,还降低了 NG 被 CD4 淋巴细胞的非特异性摄取。对于 T 淋巴瘤细胞系,载有美登素的偶联物在 17ng/mL 抗体浓度时显示出剂量依赖性的细胞生长抑制作用。另一方面,抗体药物偶联物(ADC)型抗 CD4 制剂仅在明显更高的 1.8μg/mL 浓度下才能达到类似水平的细胞生长抑制作用。NG 和抗体偶联物具有将大量有效载荷以更有效的方式递送到特定靶标的优势,因为它需要的抗体要少得多才能达到类似的效果。