Binding of monoclonal antibodies (mAbs) onto ac ell surface triggers antibody-mediated effector killing by innate immune cells through complement activation. As an alternative to mAbs,s ynthetic systems that can recruit endogenous antibodies from the blood stream to acancer cell surface could be of great relevance.H erein, we explore antibodyrecruiting polymers (ARPs) as an ovel class of immunotherapy. ARPs consist of ac ell-binding motif linked to ap olymer that contains multiple small molecule antibody-binding motifs along its backbone.A saproof of concept, we employalipid anchor that inserts into the phospholipid cell membrane and make use of apolymeric activated ester scaffold onto whichwe substitute dinitrophenol as an antibody-binding motif.W e demonstrate that ARPs allow for high avidity antibody binding and drive antibody recruitment to treated cells for several days. Furthermore,weshowthat ARP-treated cancer cells are prone to antibody-mediated killing through phagocytosis by macrophages.

The search for vaccines that protect from severe morbidity and mortality because of infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes coronavirus disease 2019 (COVID‐19) is a race against the clock and the virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting of an imidazoquinoline conjugated to the chain end of a cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It is water‐soluble and exhibits massive translocation to lymph nodes upon local administration through binding to albumin, affording localized innate immune activation and reduction in systemic inflammation. The adjuvanticity of IMDQ‐PEG‐CHOL was validated in a licensed vaccine setting (quadrivalent influenza vaccine) and an experimental trimeric recombinant SARS‐CoV‐2 spike protein vaccine, showing robust IgG2a and IgG1 antibody titers in mice that could neutralize viral infection in vitro and in vivo in a mouse model.

Triggering antibody-mediated innate immune mechanisms to kill cancer cells is an attractive therapeutic avenue.

Conjugation of nanoparticles (NP) to the surface of living cells is of interest in the context of exploiting the tissue homing properties of ex vivo engineered T cells for tumor‐targeted delivery of drugs loaded into NP. Cell surface conjugation requires either a covalent or non‐covalent reaction. Non‐covalent conjugation with ligand‐decorated NP (LNP) is challenging and involves a dynamic equilibrium between the bound and unbound state. Covalent NP conjugation results in a permanently bound state of NP, but the current routes for cell surface conjugation face slow reaction kinetics and random conjugation to proteins in the glycocalyx. To address the unmet need for alternative bioorthogonal strategies that allow for efficient covalent cell surface conjugation, we developed a 2‐step click conjugation sequence in which cells are first metabolically labeled with azides followed by reaction with sulfo‐6‐methyl‐tetrazine‐dibenzyl cyclooctyne (Tz‐DBCO) by SPAAC, and subsequent IEDDA with trans‐cyclooctene (TCO) functionalized NP. In contrast to using only metabolic azide labeling and subsequent conjugation of DBCO‐NP, our 2‐step method yields a highly specific cell surface conjugation of LNP, with very low non‐specific background binding.

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