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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3795-3803.
Prepublished online as a Blood First Edition Paper on January 10, 2006; DOI 10.1182/blood-2005-10-3945.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
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 Nash, and
Massimo Aglietta
From the Division of Medical Oncology, Laboratory of Tumor Immunology, Unit of Radiation Therapy, Laboratory of Clinical and Experimental Cytometry, and Unit of Pathology, Institute for Cancer Research and Treatment, Candiolo, Turin, Italy; Bone Marrow Transplantation Unit, University of Milan, Ospedale Maggiore, Italy; Department of Oncology, Transplant and Advances in Medicine, University of Pisa, Italy; Fred Hutchinson Cancer Research Center and University of Washington Medical School, Seattle, WA; and Department of Oncological Sciences, University of Turin Medical School, Italy.
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.
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