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Immunopharmacology and Targeted Therapy Laboratory

Welcome to the Immunopharmacology and Targeted Therapy Laboratory (ITTL)

 

Michael G. Rosenblum, M.S. Ph.D., Senior Professor and Director

Michael Rosenblum, M.S., Ph.D. | Senior Professor and Director

Our Investigational Therapeutic Technologies (ITT) research program centers on the design, production, purification, and characterization of innovative, cell-targeted therapeutic proteins for cancer treatment.

Employing a Concept to Clinic approach, we identify crucial biological targets on tumor cells and subsequently develop novel therapeutics that bind to these targets. This enables the specific delivery of highly cytotoxic cytokines, such as Tumor Necrosis Factor (TNF) and Interferon (IFN), or human pro-apoptotic molecules like Bax.

Recently, our laboratory has successfully engineered a novel, synthetic antibody capable of delivering biologically-active human serine protease, Granzyme B, to target and eliminate cancer cells.

  • Novel, patented synthetic antibody-GrB configuration

  • Fully human GrB protein fused to human synthetic targeting antibody fragment

  • GrB conjugate is internalized through antigen mediated endocytosis and delivers payload into cancer cell cytosol

    • No cleavage required to release conjugate

  • GrB activity is not impacted by multidrug resistance

    • Bypasses MDR/MRP and crossover to tumor chemo-resistance mechanisms

  • Dimerization by the IgG fragment increases size to 160 kDa

    • Extends half-life (~35 hrs)

    • Results in higher drug accumulation in tumors

  • Universal use of GrB with any targeting antibody or fragment

  • One-step manufacturing process producing GrB biological conjugates using existing antibodies and ligands

 GrB Protein
Our research encompasses molecular design, DNA construction, mammalian cell expression, and protein isolation and purification. Furthermore, the laboratory conducts molecular mechanistic studies in vitro, in vivo efficacy models utilizing human tumors transplanted into nude mice, pharmacokinetic analysis, and toxicity assessments. Finally, we are actively involved in clinical trial design and the clinical assessment of these targeted therapeutic agents. The laboratory group performs many of these studies at the Institute of Biosciences and Technology (IBT) and fosters extensive collaborations with research groups within the Texas Medical Center and with researchers across the United States. The ITT laboratory also maintains numerous collaborations with various commercial entities.