|Evaluation of Cellular Targeting by Fab' vs Full-Length Antibodies in Antibody-Nanoparticle Conjugates (ANCs) Using CD4 T-cells.
|Year of Publication
|Singh, K, Canakci, M, Kanjilal, P, Williams, N, Shanthalingam, S, Osborne, BA, Thayumanavan, S
|2022 03 16
|Antibodies, Monoclonal, CD4-Positive T-Lymphocytes, Immunoconjugates, Immunoglobulin Fab Fragments, Nanoparticles
Targeted delivery of chemotherapeutic drugs can improve their therapeutic efficiency by localizing their toxic effects at the diseased site. This is often achieved either by direct conjugation of drugs to antibodies targeting overexpressed receptors on cancer cells (antibody-drug conjugates/ADCs) or by conjugating antibodies to nanoparticles bearing drugs (antibody-nanoparticle conjugates/ANCs). Here, we report a platform for utilizing hinge cysteines on antigen-binding fragment (Fab') of an anti-CD4 antibody for site-specific conjugation to nanoparticles giving rise to anti-CD4 Fab'-nanoparticle conjugates (Fab'-NCs). We demonstrate a convenient route for obtaining functional anti-CD4 Fab' from full-length antibody and examine the targeted delivery efficiencies of anti-CD4 Fab'-NCs vs ANCs for selective delivery to CD4 mT-ALL cells. Our results indicate that higher avidity of full-length anti-CD4 antibody, i.e., protein alone translated to higher binding ability to CD4 mT-ALL cells in comparison with anti-CD4 Fab' alone. However, the targeted delivery efficiency of anti-CD4 Fab'-NCs was comparable to ANCs indicating that the avidity of Fab' is restored in a nanoparticle-conjugate format. Fab'-NCs are equally capable of achieving targeted drug delivery to CD4 T-cells as ANCs and are a versatile alternative to ANCs by offering site-selective modification strategy while retaining their advantages.
|PubMed Central ID
|R35 GM136395 / GM / NIGMS NIH HHS / United States
T32 GM108556 / GM / NIGMS NIH HHS / United States