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Antigenic modulation by anti-CD5 immunotoxins.

J M Manske, D J Buchsbaum, S M Azemove

    Journal of Immunology (Baltimore, Md. : 1950)
    |June 15, 1986
    PubMed
    Summary
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    The presence of toxin on T101 immunotoxins enhances CD5 modulation on leukemic cells. This modulation is key for T101 immunotoxin internalization and therapeutic potential.

    Area of Science:

    • Immunology
    • Cell Biology
    • Biochemistry

    Background:

    • Antigenic modulation is a critical factor in monoclonal antibody therapy.
    • Understanding immunotoxin (IT) behavior is essential for targeted cancer therapies.

    Purpose of the Study:

    • To evaluate the effect of toxin conjugation on T101 immunotoxin (IT) antigenic modulation of CD5.
    • To determine the fate of T101 IT bound to leukemic cells.

    Main Methods:

    • Conjugating T101 antibody to intact ricin or ricin A chain to create IT.
    • Assessing CD5 modulation efficiency and protein synthesis inhibition.
    • Utilizing radiolabeled reagents (125I) to track IT internalization and shedding.

    Main Results:

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  • T101-A chain demonstrated more efficient CD5 modulation than T101-ricin and T101 alone.
  • T101-ricin exhibited significant protein synthesis inhibition (99%), while T101-A chain showed lower toxicity (23-43%).
  • Monensin enhanced T101-A chain toxicity but not its modulation; both T101 and T101-ricin were internalized.

    • Conclusions:

    • Toxin presence enhances, not inhibits, T101 IT modulation.
    • T101 IT are internalized, and modulation may be advantageous for IT therapy.
    • T101-A chain's low toxicity is not due to modulation deficiency.