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Identification and elimination of immunodominant T cell epitope in a recombinant immunotoxin used to treat cancer

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NCI

IMMUNO-17

Authors

  • R. Mazor
  • J. Eberle
  • A. Vassall
  • R. Beers
  • X. Hu
  • I. Benhar
  • I. Pastan

Abstract

Moxetumomab pasudotox and SS1P are immunotoxins that have been developed in our lab to treat cancer. This talk described identification and elimination of T cell epitopes in the bacterial moiety of immunotoxins. We used an vitro stimulation step with the whole protein which specifically expands T-cell populations that are reactive to naturally processed peptide, followed by ELISpot. This strategy had a 100% response rate which correlates with the immunogenicity response rate of patients that have been treated with immunotoxin. We identified one highly-reactive and immunodominant epitope that stood out among multiple subdominant epitopes and constructed mutant RITs that retained cytotoxic activity, and had reduced T-cell immunogenicity.

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