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Clin Cancer Res 2006 Aug 1;12(15):4678-86

Intratumoral Therapy with IL13-PE38 Results in Effective CTL-Mediated Suppression of IL-13R{alpha}2-Expressing Contralateral Tumors.

Kawakami K, Terabe M, Kioi M, Berzofsky JA, Puri RK

Kawakami K, Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Sakyo Ku, Yoshida Konoecho, Kyoto 6068501, Japan US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Tokyo, Japan

Abstract

PURPOSE: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13Ralpha2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response. EXPERIMENTAL DESIGN: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13Ralpha2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only. Results and CONCLUSIONS: When animals with IL-13Ralpha2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13Ralpha2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8(+) T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response.


Category: Journal Article
PubMed ID: #16899618
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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