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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Experimental Hematology & Oncology 1/2018

WT1 peptide vaccine in Montanide in contrast to poly ICLC, is able to induce WT1-specific immune response with TCR clonal enrichment in myeloid leukemia

Zeitschrift:
Experimental Hematology & Oncology > Ausgabe 1/2018
Autoren:
Hongtao Liu, Yuanyuan Zha, Noura Choudhury, Gregory Malnassy, Noreen Fulton, Margaret Green, Jae-Hyun Park, Yusuke Nakamura, Richard A. Larson, Andres M. Salazar, Olatoyosi Odenike, Thomas F. Gajewski, Wendy Stock

Abstract

Background

The optimal strategy for vaccination to induce CD8+ T cell responses against WT1 is not known.

Methods

A pilot randomized study in HLA-A02+ patients to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to explore the novel immune adjuvant was conducted. Seven patients were randomized. Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five patients were in morphologic remission and two had residual morphologic disease at the study entry.

Results

All patients finished the induction phase without any major toxicity except mild transient local injection reaction. One patient on the Montanide arm developed aseptic ulceration at two vaccine sites which healed without antibiotics. Three of 4 patients on the Montanide arm had a decreased expression of WT1 after WT1 vaccination, and two of them demonstrated generation of WT1-specific cytotoxic CD8+ T cell responses with biased TCR beta chain enrichment. In contrast, no obvious WT1-specific immune responses were detected in two patients on the poly ICLC arm, nor was there clonal enrichment by TCR alpha/beta sequencing; however, these patients did also have decreased WT1 expression and remained in remission several years after the initiation of treatment.

Conclusions

WT1 peptide vaccine with Montanide as an adjuvant induces detectable WT1-specific CD8+ T cell responses with clonal TCR enrichment, which may be capable of controlling leukemia recurrence in the setting of minimal residual disease. Poly ICLC may induce anti-leukemic activity in the absence of detectable WT1 specific CD8+ T cell responses.
Trial registration NCT01842139, 7/3/2012 retrospectively registered; https://​clinicaltrials.​gov/​ct2/​show/​NCT01842139.
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