Related Experiment Video
Updated: Jan 29, 2026
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
A proimmunotoxin nanodrug targeting AIDS-associated non-Hodgkin lymphoma
Shilin Chen1, Tong Qi1, Hongxu Peng2
1Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA; UCLA AIDS Institute, Los Angeles, CA, USA; Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA, USA.
B-cell non-Hodgkin lymphoma (NHL) is the most common hematopoietic malignancy in the United States, with a notably higher incidence and aggressiveness observed in individuals infected with human immunodeficiency virus (HIV), leading to AIDS-associated NHL (AIDS-NHL). The transferrin receptor 1 (TfR1/CD71), a type II transmembrane homodimeric protein, is overexpressed on several cancers, including NHL, providing a meaningful therapeutic target. Our group developed an anti-TfR1 IgG3-avidin fusion protein, ch128.1Av, designed to deliver biotinylated therapeutic agents into cancer cells through receptor-mediated endocytosis. When coupled with biotinylated saporin 6 (b-SO6), a plant-derived protein synthesis inhibitor, the resulting ch128.1Av/b-SO6 immunotoxin is highly effective at killing malignant cells. However, toxicity to normal cells limits its systemic administration. To overcome this problem, we developed a proimmunotoxin nanodrug, named "n(ch128.1Av/b-SO6)-CXCL13". This strategy involves encapsulating individual immunotoxins within a thin zwitterionic polymer shell, which is stabilized by peptide crosslinkers that only respond to metalloproteinase-2 (MMP-2), a tumor microenvironment-specific enzyme. The nanodrug is further conjugated with a B-cell targeting chemokine CXCL13. This design allows the proimmunotoxin to circulate safely, specifically accumulate and release encapsulated ch128.1Av/b-SO6 intratumorally in response to MMP-2. This approach not only minimizes off-target toxicity but also enhances tissue penetration by enabling choline analogues on proimmunotoxin nanodrugs to bind choline transporters expressed on tumor cells or the blood-brain barrier. Importantly, n(ch128.1Av/b-SO6)-CXCL13 demonstrated antitumor efficacy in an AIDS-associated NHL xenograft mouse model. Taken together, our results suggest that n(ch128.1Av/b-SO6)-CXCL13, or similar proimmunotoxin strategies, represents a promising therapeutic avenue for AIDS-NHL and potentially other malignancies.
B-cell non-Hodgkin lymphoma (NHL) is the most common hematopoietic malignancy in the United States, with a notably higher incidence and aggressiveness observed in individuals infected with human immunodeficiency virus (HIV), leading to AIDS-associated NHL (AIDS-NHL). The transferrin receptor 1 (TfR1/CD71), a type II transmembrane homodimeric protein, is overexpressed on several cancers, including NHL, providing a meaningful therapeutic target. Our group developed an anti-TfR1 IgG3-avidin fusion protein, ch128.1Av, designed to deliver biotinylated therapeutic agents into cancer cells through receptor-mediated endocytosis. When coupled with biotinylated saporin 6 (b-SO6), a plant-derived protein synthesis inhibitor, the resulting ch128.1Av/b-SO6 immunotoxin is highly effective at killing malignant cells. However, toxicity to normal cells limits its systemic administration. To overcome this problem, we developed a proimmunotoxin nanodrug, named "n(ch128.1Av/b-SO6)-CXCL13". This strategy involves encapsulating individual immunotoxins within a thin zwitterionic polymer shell, which is stabilized by peptide crosslinkers that only respond to metalloproteinase-2 (MMP-2), a tumor microenvironment-specific enzyme. The nanodrug is further conjugated with a B-cell targeting chemokine CXCL13. This design allows the proimmunotoxin to circulate safely, specifically accumulate and release encapsulated ch128.1Av/b-SO6 intratumorally in response to MMP-2. This approach not only minimizes off-target toxicity but also enhances tissue penetration by enabling choline analogues on proimmunotoxin nanodrugs to bind choline transporters expressed on tumor cells or the blood-brain barrier. Importantly, n(ch128.1Av/b-SO6)-CXCL13 demonstrated antitumor efficacy in an AIDS-associated NHL xenograft mouse model. Taken together, our results suggest that n(ch128.1Av/b-SO6)-CXCL13, or similar proimmunotoxin strategies, represents a promising therapeutic avenue for AIDS-NHL and potentially other malignancies.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:22Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
02:22Regulated mRNA Transport
02:26Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:58Fruit Development, Structure, and Function