Instant immunity through chemically programmable vaccination and covalent self-assembly

Abstract

The ability to instantly create a state of immunity as achieved in the passive transfer of hyperimmune globulin has had a tremendous impact on public health. Unlike passive immunization, active immunization, which is the foundation of vaccinology, is an anticipatory strategy with inherent limitations. Here we show that elements of active and passive immunization can be combined to create an effective chemistry-driven approach to vaccinology. Reactive immunization was used to create a reservoir of covalent polyclonal antibodies in 3 mouse strains that were subsequently engrafted with syngeneic CT26 colon or B16F10 melanoma tumors. Upon administration of designed integrin ␣v␤3 and ␣v␤5 adapter ligands, the induced covalent polyclonal antibodies self-assembled with the adapter ligands and the animals mounted an instant, chemically programmed, polyclonal response against the implanted tumors. Significant therapeutic responses were observed without recourse to adjuvant therapy. The chemically programmed immune responses were driven by antibody-dependent cellular cytotoxicity and complement-directed cytotoxicity. We suggest that this type of chemistry-driven approach to vaccinology is underexplored and may provide routes to vaccines to protect against diseases that have proven intractable to biology-driven vaccine approaches.aldolase ͉ angiogenesis ͉ colon cancer ͉ melanoma ͉ tolerance

Effective Molarity Redux: Proximity as a Guiding Force in Chemistry and Biology

“…In an ambitious manifestation of proximity-induced reactions, Spiegel and Barbas, building on early precedent of Schultz, [25] made use of proximity to specify a sophisticated immune response as opposed to degradation of a single protein, [26] Using antibody recruiting molecules (ARMs) possessing an antibody binding motif and a target cell binding motif, it has been possible to target HIV positive cells, [27] prostate cancer cells, [28] and metastatic cancer cells. [29] This approach goes beyond simply rewiring signaling enzyme specificity, but it utilizes the same concepts, such as ternary complex formation to bring biomolecules in proximity to change biological output.…”

Reprogramming Urokinase into an Antibody-Recruiting Anticancer Agent

“…(50,51,52,53,54) Despite these successes, relatively few examples of using small-molecules to redirect antibody-mediated immune responses against cancers have been disclosed. (28,29,30,31,32,33,34,35) Some of these approaches have shown promising results in animal studies using anti-hapten-immunized mice(29,30,35,55) or with injected antibody(31,32,33). The approach reported here differs from these prior strategies in that it targets uPAR, which is found on a broad variety of invasive cancer cells, and it also has the potential to exploit the naturally-occurring, hapten-directed class of anti-DNP antibodies for cancer cell destruction.…”

β-Diketone modified trastuzumab: A next-generation of Herceptin for resistant breast cancer cells?

“…Recently, Popkov et al have developed a strategy named ''instant immunity'' [13,14], which is promising in cancer therapy. According to the strategy, a vaccine to induce the antibody scaffold was firstly immunized with chemicals such as b-diketone, then this chemical linked small molecules or peptides which can trace the disease specific targets were injected to the antibody.…”