Targeting CD4+ Cells with Anti-CD4 Conjugated Mertansine-Loaded Nanogels

Biomacromolecules. 2020 Jun 8;21(6):2473-2481. doi: 10.1021/acs.biomac.0c00442. Epub 2020 May 28.

Abstract

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 CD4high 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents*
  • CD4-Positive T-Lymphocytes
  • Immunoconjugates*
  • Maytansine*
  • Nanogels

Substances

  • Antineoplastic Agents
  • Immunoconjugates
  • Nanogels
  • Maytansine