AI Article Synopsis

  • Immunotoxins (ITs) like ricin and pulchellin are being explored as treatments for cancer and chronic infections, utilizing antibodies linked to toxins for targeted cell killing.
  • The study compared ricin-derived A chains (RAC) with pulchellin-derived A chains (PAC) to assess their effectiveness in killing HIV-infected cells, with both obtaining a successful chemical conjugation to anti-HIV antibodies.
  • Results indicated that while PAC shows potential as an effective immunotoxin, its cytotoxicity is somewhat less than that of the ricin standard, providing a foundation for further development in targeted therapies.

Article Abstract

Immunotoxins (ITs), which consist of antibodies conjugated to toxins, have been proposed as a treatment for cancer and chronic infections. To develop and improve the ITs, different toxins such as ricin, have been used, aiming for higher efficacy against target cells. The toxin pulchellin, isolated from the Abrus pulchellus plant, has similar structure and function as ricin. Here we have compared two plant toxins, recombinant A chains from ricin (RAC) and pulchellin (PAC) toxins, for their ability to kill HIV Env-expressing cells. In this study, RAC and PAC were produced in E. coli, and chromatographically purified, then chemically conjugated to two different anti-HIV monoclonal antibodies (MAbs), anti-gp120 MAb 924 or anti-gp41 MAb 7B2. These conjugates were characterized biochemically and immunologically. Cell internalization was studied by flow cytometry and confocal microscopy. Results showed that PAC can function within an effective IT. The ITs demonstrated specific binding against native antigens on persistently HIV-infected cells and recombinant antigens on Env-transfected cells. PAC cytotoxicity appears somewhat less than RAC, the standard for comparison. This is the first report that PAC may have utility for the design and construction of therapeutic ITs, highlighting the potential role for specific cell targeting.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548917PMC
http://dx.doi.org/10.1038/s41598-017-08037-3DOI Listing

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