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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Gururaj Shivange1, Tanmoy Mondal1, Evan Lyerly1
1Laboratory of Novel Biologics, University of Virginia School of Medicine; Department of Biochemistry and Molecular Genetics, UVA Cancer Center, University of Virginia School of Medicine.
Abstract:
Monoclonal antibodies are high affinity multifunctional drugs that work by variable independent mechanisms to eliminate cancer cells. Over the last few decades, the field of antibody-drug conjugates, bispecific antibodies, chimeric antigen receptors (CAR) and cancer immunotherapy has emerged as the most promising area of basic and therapeutic investigations. With numerous successful human trials targeting immune checkpoint receptors and CAR-T cells in leukemia and melanoma at a breakthrough pace, it is highly exciting times for oncologic therapeutics derived from variations of antibody engineering. Regrettably, a significantly large numbers of antibody and CAR based therapeutics have also proven disappointing in human trials of solid cancers because of the limited availability of immune effector cells in the tumor bed. Importantly, nonspecific distribution of therapeutic antibodies in tissues other than tumors also contribute to the lack of clinical efficacy, associated toxicity and clinical failure. As faithful translation of preclinical studies into human clinical trails are highly relied on mice tumor xenograft efficacy and safety studies, here we highlight a method to test the tumor and general tissue distribution of therapeutic antibodies. This is achieved by labeling the protein-A purified antibody with near Infrared fluorescent dye followed by live imaging of tumor bearing mice.
Insights
Researchers developed a novel method using near-infrared fluorescent dyes to track therapeutic antibody distribution in tumors and tissues. This technique aids in evaluating antibody-drug conjugates and CAR-T cell therapies for cancer treatment efficacy and safety.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacokinetics
- Antibody Engineering
Background:
- Monoclonal antibodies and engineered cell therapies (CAR-T) show promise in treating blood cancers but face challenges in solid tumors.
- Limited immune cell infiltration and nonspecific antibody distribution in solid tumors hinder clinical efficacy and increase toxicity.
- Accurate assessment of therapeutic antibody biodistribution is crucial for translating preclinical findings to clinical success.
Purpose of the Study:
- To present a method for evaluating the tumor and general tissue distribution of therapeutic antibodies.
- To improve the preclinical assessment of antibody-based cancer therapies, including antibody-drug conjugates and CAR-T cells.
Main Methods:
- Protein-A purified therapeutic antibodies were labeled with a near-infrared fluorescent dye.
- Live imaging techniques were employed to visualize antibody distribution in tumor-bearing mice.
- This method allows for the assessment of antibody distribution in both tumor sites and off-target tissues.
Main Results:
- The near-infrared fluorescent labeling enabled clear visualization of antibody distribution.
- This technique allows for the quantitative and qualitative assessment of antibody uptake in tumors versus healthy tissues.
- Demonstrated feasibility of tracking antibody biodistribution in vivo for preclinical evaluation.
Conclusions:
- This near-infrared fluorescent imaging method provides a valuable tool for assessing therapeutic antibody distribution in preclinical cancer models.
- Improved understanding of antibody biodistribution can help optimize antibody-based therapies and reduce off-target toxicity.
- Facilitates more reliable translation of promising antibody and CAR-T cell therapies from bench to bedside for solid tumors.
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