The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma

Our plain-English summary of The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma, by A.K. Iyer, Y. Su, J. Feng, et al (Biomaterials, 2011).

The study

• Authors: A.K. Iyer, Y. Su, J. Feng, X. Lan, X. Zhu, Y. Liu, D. Gao, Y. Seo, H.F. Vanbrocklin, V. Courtney Broaddus, B. Liu, J. He
• Journal: Biomaterials
• Published: 2011;32(10):2605-13
• Cited by: 35 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with (111)In ((111)In-IL-M1), along with control non-targeted liposomes ((111)In-CL). Incubation of (111)In-IL-M1 with M28, VAMT-1, and a control non-tumorigenic cell line (BPH-1) at 37 °C for 24 h revealed efficient binding and rapid internalization of ILs into both subtypes of tumor cells but not into the BPH-1 cells; internalization accounted for approximately 81-94% of total cell accumulation in mesothelioma cells compared to 37-55% in control cells. In tumor-bearing mice intravenous (i.v.) injection of (111)In-IL-M1 led to remarkable tumor accumulation: 4% and 4.7% injected dose per gram (% ID/g) for M28 and VAMT-1 tumors, respectively, 48 h after injection. Furthermore, tumor uptake of (111)In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of (111)In-CL in tumor-bearing mice revealed very low uptake in both subtypes of mesothelioma, 48 h after injection. In conclusion, M1 scFv-anchored ILs showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid subtypes of human mesothelioma, demonstrating its potential as a promising vector for enhanced tumor drug targeting.

Copyright © 2010 Elsevier Ltd. All rights reserved.

In plain English

This laboratory and mouse study did not involve asbestos exposure. It tested tiny fat-based particles (liposomes) that carried an antibody fragment, M1 scFv, designed to attach to mesothelioma cells. The particles were tagged with radioactive indium-111. They were tested on two human mesothelioma cell lines, M28 (epithelioid) and VAMT-1 (sarcomatoid), and on BPH-1, a control line that does not form tumors. Uptake into cells rose with more antibody per particle up to about 50 to 60, then leveled off. After 24 hours, the radioactivity bound to and taken into cells, counted as a percentage of the radioactivity added per million cells, was above 85% for both mesothelioma lines and below 35% for control cells. In mice, tumor uptake 48 hours after injection was 4.01 (M28) and 4.69 (VAMT-1) percent of the injected dose per gram. Particles without the antibody gave 0.97 and 0.4. Uptake was also high in the liver (7.97 at 48 hours, above either tumor) and the spleen (4.06). The authors concluded that the particles showed selective targeting of both subtypes and promise for imaging and therapy. They noted that questions about use in patients remain.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory cell-culture experiments and an animal experiment (mouse tumor xenograft model with biodistribution and SPECT/CT imaging)
• Who was studied: Human mesothelioma cell lines M28 (epithelioid) and VAMT-1 (sarcomatoid), a control non-tumorigenic cell line (BPH-1), and six-week-old male nu/nu mice carrying both tumor types. Mice were in groups of 4 (targeted particles) or 3 (control particles). The work was done at the University of California at San Francisco.
• Exposure: No asbestos exposure was studied. The test agent was indium-111-labeled immunoliposomes carrying M1 scFv antibody fragments (about 50 per vesicle, called 111In-IL-M1(50)). These were compared with non-targeted control liposomes (111In-CL).
• Main results:
  • In VAMT-1 cells, internalization rose as antibody density per vesicle increased, up to about 50 to 60 scFv per vesicle, and then plateaued.
  • Cell radioactivity was expressed as a percentage of the applied activity, normalized to 1 million cells. After 24 hours, the amount bound and internalized was above 85% for both mesothelioma cell lines, compared with below 35% for the control BPH-1 cells.
  • In mesothelioma cells, the internalized share of the total bound radioactivity was about 90%.
  • In mice at 48 hours, tumor uptake of the targeted particles was 4.01 (SD 0.39) and 4.69 (SD 0.72) percent injected dose per gram for M28 and VAMT-1 tumors. This was higher than all other organs studied except the liver, which was 7.97 (SD 0.34).
  • Spleen uptake of the targeted particles at 48 hours was 4.06 percent injected dose per gram. At 24 hours it was 8.87, and liver uptake was 15.69.
  • Control non-targeted liposomes showed tumor uptake of 0.97 (SD 0.48) and 0.4 (SD 0.42) percent injected dose per gram for M28 and VAMT-1 tumors at 48 hours.
  • At 48 hours, tumor-to-blood ratios were 31:1 (M28) and 36:1 (VAMT-1), and tumor-to-muscle ratios were 47:1 and 55:1.
  • SPECT/CT imaging at 24 hours showed marked uptake into both tumor types and also high uptake in the liver and spleen.
• The authors' conclusion: The authors concluded that the M1 scFv-anchored immunoliposomes showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid mesothelioma, in cells and in mice. They saw potential for delivering drugs and radionuclides for imaging and therapy.
• Limitations the authors state:
  • The low PEG content of the particles shortened their circulation time in the blood.
  • In patients, the particles' ability to reach the target may vary depending on whether the target is accessible from the blood vessels.
  • In vivo stability, half-life, possible immune response, and uptake by the liver and spleen system still need evaluation.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Sarcomatoid, Mesothelioma.

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