Toward Anticancer Immunotherapeutics: Well‐Defined Polymer–Antibody Conjugates for Selective Dendritic Cell Targeting

Abstract

This paper describes the synthesis of semitelechelic maleimide-modified N-(2-hydroxypropyl)methacrylamid) (HPMA) based polymers of narrow dispersity that can be conjugated e.g. to anti-DEC-205 antibodies affording "star-like" topologies (one antibody decorated with several polymer chains). FCS revealed a hydrodynamic diameter of R(h) = 7.9 nm and SEC narrow dispersity (1.45). Primary in vitro studies with bone marrow derived dendritic cells (DC) show higher cellular binding and uptake rates compared to control samples. Moreover, incubating these conjugates to primary splenocytes demonstrates a much higher affinity to the primary DCs than to any other immune cell population within the spleen. This differentiation is, thereby, much more pronounced for the star-like conjugates than for conjugates made from polymers statistically modified with anti-DEC-205.

Not Just for Tumor Targeting: Unmet Medical Needs and Opportunities for Nanomedicine

“…Thereby, the polymers' topology has a significant influence on the specificity of their site-specific uptake into CD8 + DCs, even in the presence of macrophages [51]. Considering the numerous possibilities of functionalizing such HPMA carriers with further tumor-relevant antigens (e.g., MUC1-derived glycopeptide antigens as shown above) [33] cellular MUC1-derived antitumor response should be feasible too [52].…”

Nanoparticles and the Immune System: Challenges and Opportunities

“…In such a complex mixture of proteins it turned out that the formation of a protein corona is likely to occur for many nanoparticles and its composition relates to the material used to construct the carrier systems and thus cannot be disregarded whenever the behavior of the whole system is investigated [16]. Nevertheless, a successful targeting of immune cells seems possible [17,18]. To that respect, the potential of nanoparticles for immunotherapyin general -is enormous [19,20] or, in other words 'The immune system likes nanotechnology' [21,22].…”

HPMA Copolymer–Drug Conjugates with Controlled Tumor‐Specific Drug Release

“…In addition to soluble polymer–drug conjugates, this technology supports the synthesis of amphiphilic block copolymers that form micellar structures in aqueous solutions . This technology can also be used to create versatile and targeted drug carriers for sophisticated molecular imaging and tumor immunotherapy …”