Macromolecular therapeutics that selectively trigger cancer cell suicide via clustering a range of target receptors with no toxins. Preclinical evidence suggests broad applicability.

This Drug-Free Macromolecular Therapeutic (DFMT) technology represents a new paradigm for inducing cell death based on the crosslinking of cell-surface receptors in B cell malignancies. This crosslinking induces apoptosis independent of effector cells from the immune system. Selectivity for malignant cells is based on biorecognition by high-fidelity natural binding motifs that include antiparallel coiled-coil peptides or complementary oligonucleotides. This technology combines the activation pathways of Type I and Type II antibodies into one system to enhance apoptosis through multiple mechanisms.

This technology is related to U-6028.

Optimization & Testing

• No cytotoxic compounds required to induce tumor cell death which can avoid many of the side effects commonly seen with chemotherapies.
• DFMT has the potential to overcome rituximab resistance and sensitize cells for other drug-based therapies.
• Albumin nanoconjugates facilitate the manufacturing process and provide an extended intravascular half-life.
• Retains effectiveness against high risk mutations with poor prognoses.

• Chu T, Zhang R, Yang J, et al (2015). A Two-Step Pretargeted Nanotherapy for CD20 Crosslinking May Achieve Superior Anti-Lymphoma Efficacy to Rituximab. Theranostics. 5(8): 834-846.
• Li L, Yang J, Wang J, et al (2018). Amplification of CD20 Crosslinking in Rituximab Resistant B-Lymphoma Cells Enhances Apoptosis Induction by Drug-Free Macromolecular Therapeutics. ACS Nano. 12(4): 3658-3670.
• Li L, Wang J, Li Y, et al (2019). Broadening and Enhancing Functions of Antibodies by Self-Assembling Multimerization at Cell Surface. ACS Nano. 13(10): 11422-11432.

Publication Number: US 2016/0015732 A1
Patent Title: Compositions and Methods for Inducing Apoptosis
Jurisdiction/Country: United States
Application Type: Non-Provisional

Jason Young
(801) 587-0519
jason.r.young@utah.edu