Tumor suppressor effect of an antibody on xenotransplanted sarcomatoid mesothelioma cells

Our plain-English summary of Tumor suppressor effect of an antibody on xenotransplanted sarcomatoid mesothelioma cells, by M. Hasegawa, Y. Hanamatsu, C. Saigo, et al (Thoracic Cancer, 2022).

The study

• Authors: M. Hasegawa, Y. Hanamatsu, C. Saigo, Y. Kito, T. Takeuchi
• Journal: Thoracic Cancer
• Published: 2022;13(18):2566-2573
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: As mesothelioma generally has an unfavorable prognosis, further advances are needed to improve the outcomes in patients with mesothelioma. In the present study, we generated and characterized a monoclonal antibody that could inhibit mesothelioma cell proliferation in a xenotransplantation mouse model.

Methods: We generated monoclonal antibodies by immunizing mice with cultured mesothelioma cells. These antibodies were then characterized by immunofluorescence staining, immunohistochemical staining, secondary antibody-drug conjugate assay, antibody inoculation in a xenotransplantation mesothelioma mouse model, and mass spectrometry followed by small interfering RNA (siRNA) analysis. 5' rapid amplification of complementary DNA ends followed by sequencing was performed to deduce the amino acid sequences of the variable regions of the light and heavy chains of AX10.

Results: An IgG2b κ-type AX10 antibody against the cell surface membrane of sarcomatoid mesothelioma cells was generated. AX10 immunoreactivity was detected in 12 out of 22 different mesothelioma tissue specimens, but there was little AX10 immunoreactivity in a normal human tissue array. AX10 decreased Matrigel invasion by MPM-1 cells but did not affect cell proliferation. Notably, AX10 significantly inhibited the proliferation of MPM-1 cells xenotransplanted into Severe combined immunodeficiency-Nonobese diabetic mice. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry followed by siRNA silencing indicated that AX10 reacted to a unique alternatively spliced isoform of sarcolemma-associated protein. AX10 is composed of as yet unregistered amino acid sequences in its variable region.

Conclusions: AX10 could have therapeutic potential for patients with sarcomatoid mesothelioma.

© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

In plain English

This was a laboratory and animal study from Gifu University, Japan. It did not study asbestos exposure. The authors immunized a mouse with cultured human mesothelioma cells to make monoclonal antibodies. They selected one, AX10, that bound the surface of four mesothelioma cell lines. AX10 reacted with 12 of 22 mesothelioma tissue specimens. The subtype figures, five of six sarcomatoid, five of 10 epithelioid and one of five biphasic, total 11 of 21; the article does not explain the difference. It showed little reaction with normal tissues, though it reacted weakly with uterine cells and strongly with one melanoma sample. In lab dishes, AX10 did not change how fast sarcomatoid MPM-1 cells multiplied but significantly reduced their invasion through a gel barrier. In immune-deficient mice carrying MPM-1 tumors, weekly AX10 injections significantly impaired tumor growth (p less than 0.01; groups of five mice). Pemetrexed, a chemotherapy drug, did not significantly suppress growth there. AX10 appeared to bind a particular form of a protein called SLMAP. The authors concluded that AX10 could have therapeutic potential for patients with sarcomatoid mesothelioma.

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 study: generation and characterization of a monoclonal antibody, with cell-culture experiments, staining of tissue microarrays, and a mouse xenograft (transplanted human tumor) experiment
• Who was studied: Four human mesothelioma cell lines (ACC-MESO-1 and MPM-1, -2, -3). Purchased tissue microarrays of mesothelioma and of normal organs. Immune-deficient SCID-NOD male mice: 10 in the main xenograft experiment (two groups of five) and 15 in the pemetrexed comparison (three groups of five).
• Exposure: Treatment with the AX10 antibody (0.25 mg weekly in mice), compared with no treatment and, in one experiment, with pemetrexed (0.5 mg). No asbestos or other fiber exposure was studied.
• Main results:
  • AX10 reacted with 12 of 22 mesothelioma tissue specimens
  • AX10 reacted strongly with five of six sarcomatoid mesothelioma tissues
  • AX10 reactivity was reported in five of 10 epithelioid and one of five biphasic mesothelioma tissues. Together with the sarcomatoid figures, these total 11 of 21, not the 12 of 22 stated overall.
  • Normal tissues: no significant reactivity in lung, including pleural mesothelial cells. The article also reports weak reactivity in uterine cells and none significant in brain, liver or kidney.
  • Strong AX10 reactivity was seen in one melanoma tissue sample included in the microarray
  • In cell culture, AX10 did not significantly affect proliferation of MPM-1 cells
  • In cell culture, AX10 significantly reduced the gel-barrier (Matrigel) invasion of MPM-1 cells (p less than 0.01)
  • When AX10 was combined with a drug-carrying secondary antibody, dose-dependent apoptosis (cell death) of MPM-1 cells was seen
  • In mice with transplanted MPM-1 tumors, AX10 injections impaired tumor growth (p less than 0.01; n = 5 mice per group)
  • Pemetrexed did not significantly suppress MPM-1 tumor growth in the mice
  • AX10 was found to bind SLMAP (sarcolemma-associated protein) in MPM-1 cells
• The authors' conclusion: The authors concluded that AX10 could have therapeutic potential for patients with sarcomatoid mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Sarcomatoid, Mesothelioma, Prognosis, Monoclonal Antibody, Immunohistochemistry.

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