ImmTORTM to amplify the efficacy and reduce immunogenicity of biologics

Abstract

In recent months as vaccines against the SARS-CoV-2 virus continue to rollout across the globe, there has been a renewed interest in ways to activate or ignite the immune system. For a vaccine to be effective, it must be immunogenic and specific to provoke the body's defenses to mount an effective response that protects the host from disease. However, there are other situations wherein the immune system mounts an unwanted immune response that can be detrimental to health, either directly, by causing an autoimmune disease, or indirectly, by compromising the safety and/or efficacy of biologic drugs. In these scenarios, it would be desirable to have a ‘tolerogenic vaccine’ that could selectively and effectively mitigate these unwanted immune responses. ImmTORTM, a nanoparticle technology, is being developed to address the issue of immunogenicity for gene therapy vectors and other biologic drugs. By targeting antigen-presenting cells, ImmTORTM has the potential to amplify the efficacy of biologic therapies and unlock the full potential of such treatments to improve the lives of those who suffer from serious and debilitating diseases.

Enhancing the Response Rate to Recombinant Uricases in Patients with Gout

“…For example, methotrexate is contraindicated in patients who have alcoholism or liver disease and must be used with caution in those with renal dysfunction [ 63 ]. For co-formulated systems such as SEL-212 (pegadricase plus SVP-rapamycin), immunomodulation is limited to rapamycin, which may not be optimal for all patients with uncontrolled gout [ 25 , 55 ]. Because the human immune system naturally weakens with age [ 64 ], pegloticase appears to be less immunogenic in older patients [ 10 ].…”

“…( c ) Exposure to a PEGylated uricase enzyme with immunomodulation (IMM) co-therapy (e.g., oral methotrexate) increases T-cell sensitivity to apoptosis, disrupting the pathway to immunogenicity. Figure adapted from Brunn et al 2021 [ 55 ]. Molecular images of uricase and PEGylated uricase enzymes are not representative of molecule shape or structure and are for illustration purposes only …”

“…Rapamycin, administered in synthetic vaccine poly (lactic-co-glycolic acid) nanoparticles (SVP-rapamycin), has been shown to attenuate antidrug antibody formation [ 39 , 55 ]. Coadministration of the rapamycin-nanoparticle complex (ImmTOR™) with free PEGylated uricase antigen (e.g., pegadricase) facilitates the induction of tolerogenic dendritic cells followed by antigen-specific regulatory T cells, leading to an immunosuppressive response (Fig.…”

“…Coadministration of the rapamycin-nanoparticle complex (ImmTOR™) with free PEGylated uricase antigen (e.g., pegadricase) facilitates the induction of tolerogenic dendritic cells followed by antigen-specific regulatory T cells, leading to an immunosuppressive response (Fig. 1 b) [ 39 , 55 ]. Further, this tolerogenic dendritic cell control inhibits B cells and T cells from producing antidrug antibodies against pegadricase via prevention of interleukin-2 production [ 39 , 56 ].…”