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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.
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Submitted October 3, 2005
Accepted December 29, 2005
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
Division of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, TO, Italy
Laboratory of Tumor Immunology, Institute for Cancer Research and Treatment, Candiolo, TO, Italy
Laboratory of Tumor Immunology, Institute for Cancer Research and Treatment, Candiolo, TO, Italy; Department of Oncological Sciences, University of Torino Medical School, Torino, Italy
Unit of Radiation Therapy, Institute for Cancer Research and Treatment, Candiolo, TO, Italy
Laboratory of Clinical and Experimental Cytometry, Institute for Cancer Research and Treatment, Candiolo, TO, Italy
Unit of Pathology, Institute for Cancer Research and Treatment, Candiolo, TO, Italy
Bone Marrow Transplantation Unit, University of Milan, Ospedale Maggiore, Milan, Italy
Department of Oncology, Transplant and Advances in Medicine, University of Pisa, Pisa, Italy
Fred Hutchinson Cancer Research Center and University of Washington Medical School, Seattle, WA, USA
Division of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, TO, Italy; Department of Oncological Sciences, University of Torino Medical School, Torino, Italy
* Corresponding author; email: alex.cignetti{at}ircc.it.
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 received HCT from HLA-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% (49-97) at day +56. Eight patients (53%) experienced grade II-IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization for greater than 90 days were observed in 1 and 3 patients, respectively. The induction of TAA-specific T-cells was evaluated with a CEA-specific HLA-A*0201-pentamer in 6 patients. CEA-specific CD8+ T-cells were detected in 3/3 patients concomitant with GHVD onset, but were not detected in 3/3 patients who did not develop GVHD and in 9/9 control patients with GVHD transplanted for a diagnosis 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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