Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: Tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD

Fabrizio Carnevale-Schianca, Alessandro Cignetti, Antonio Capaldi, Katiuscia Vitaggio, Antonella Vallario, Alberto Ricchiardi, Elisa Sperti, Renato Ferraris, Marco Gatti, Giovanni Grignani, Delia Rota-Scalabrini, Massimo Geuna, Marco Fizzotti, Dario Sangiolo, Antonino Sottile, Giovanni De Rosa, Anna Rosa Bucci, Giorgio Lambertenghi-Deliliers, Edoardo Benedetti, Richard NashMassimo Aglietta

Research output: Contribution to journalArticle

Abstract

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day +56. Eight patients experienced grades II to IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A*0201 pentamer in 6 patients with CRC. CEA-specific CD8+ T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response. Thus, graft-versus-host reactions associated with allogeneic HCT can trigger the generation of T cells specific for CEA, and this may be associated with a clinical response.

Original languageEnglish
Pages (from-to)3795-3803
Number of pages9
JournalBlood
Volume107
Issue number9
DOIs
Publication statusPublished - May 1 2006

ASJC Scopus subject areas

  • Hematology

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