Broadly Applicable Bispecific Linker Approach to Noncovalently Target Therapeutic Nanoparticles to Tumor Cells Expressing Carcinoembryonic Antigen.

Design strategies that lead to a more focused in vivo delivery of functionalized nanoparticles (NPs) and their cargo can potentially maximize their therapeutic efficiency while reducing systemic effects, broadening their clinical applications. Here, we report the development of a noncovalent labeling approach where immunoglobulin G (IgG)-decorated NPs can be directed to a cancer cell using a simple, linear bispecific protein adaptor, termed MFE23-ZZ. MFE23-ZZ was created by fusing a single-chain fragment variable domain, termed MFE23, recognizing carcinoembryonic antigen (CEA) expressed on tumor cells, to a small protein ZZ module, which binds to the Fc fragment of IgG.

The IgV domain of the poliovirus receptor alone is immunosuppressive and binds to its receptors with comparable affinity.

PVR (poliovirus receptor) functions as a ligand that signals through TIGIT and CD96 to induce suppression of T-cell and NK-cell responses. Alternatively, PVR binds to CD226, resulting in a co-stimulatory signal. To date, TIGIT antibody antagonists have been developed to restore immune functions and allow PVR to signal though CD226 in the context of cancer immunotherapy.

A soluble activator that favors the ex vivo expansion of CD8+CD27+ T cells.

Adoptive cell therapy involves the infusion of tumor-reactive T cells into patients with cancer to provide antitumor immunity. The ex vivo expansion and differentiation of such T cells are key parameters that affect their therapeutic potential. Human T cells are presently expanded in culture through the use of anti-CD3 and anti-CD28 mAbs immobilized on beads, expressed on cells, or assembled in the context of soluble antibody complexes.