EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells.

Published

Journal Article

PURPOSE: Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Pseudomonas-based immunotoxins have a direct cytotoxic effect. However, delayed and often dramatic antitumor responses seen in human studies with targeted toxins led us to hypothesize that immunologic responses may be a secondary mechanism that enhances the therapeutic efficacy of these novel drugs. EXPERIMENTAL DESIGN: This hypothesis was tested in a murine system using an immunotoxin, MR1-1 [MR1-1(dsFv)-PE38KDEL], that targets a syngeneic murine homologue of the tumor-specific human epidermal growth factor mutation, EGFRvIII, expressed on a murine cell line. RESULTS: Intratumoral treatment with MR1-1 eliminated EGFRvIII-expressing tumors (P < 0.0001). The antitumor activity of MR1-1 was dependent on the expression of EGFRvIII on some, but not all tumors cells, and was significantly inhibited in the absence of CD4+ (P = 0.0193) and CD8+ (P = 0.0193) T cells. MR1-1 induced EGFRvIII-specific immunity (P < 0.0005) and produced long lasting immunity against tumors expressing EGFRvIII as well as EGFRvIII-negative tumors. CONCLUSIONS: These data suggest that immunotoxins may not be strictly dependent on direct cytotoxicity for their efficacy, but may also be potent inducers of antitumor immunity active even against cells that do not express the targeted antigen.

Full Text

Duke Authors

Cited Authors

  • Ochiai, H; Archer, GE; Herndon, JE; Kuan, C-T; Mitchell, DA; Bigner, DD; Pastan, IH; Sampson, JH

Published Date

  • January 2008

Published In

Volume / Issue

  • 57 / 1

Start / End Page

  • 115 - 121

PubMed ID

  • 17634939

Pubmed Central ID

  • 17634939

International Standard Serial Number (ISSN)

  • 0340-7004

Digital Object Identifier (DOI)

  • 10.1007/s00262-007-0363-7

Language

  • eng

Conference Location

  • Germany