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

• Published in: Blood Vol. 107; no. 9; pp. 3795 - 3803
• Main Authors: Carnevale-Schianca, Fabrizio, Cignetti, Alessandro, Capaldi, Antonio, Vitaggio, Katiuscia, Vallario, Antonella, Ricchiardi, Alberto, Sperti, Elisa, Ferraris, Renato, Gatti, Marco, Grignani, Giovanni, Rota-Scalabrini, Delia, Geuna, Massimo, Fizzotti, Marco, Sangiolo, Dario, Sottile, Antonino, De Rosa, Giovanni, Bucci, Anna Rosa, Lambertenghi-Deliliers, Giorgio, Benedetti, Edoardo, Nash, Richard, Aglietta, Massimo
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.2006; The Americain Society of Hematology
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Carcinoembryonic Antigen; Case-Control Studies; Colonic Neoplasms - immunology; Colonic Neoplasms - secondary; Colonic Neoplasms - therapy; Emergency and intensive respiratory care; Female; Gastroenterology. Liver. Pancreas. Abdomen; Graft vs Host Disease - immunology; Graft vs Tumor Effect - immunology; Hematopoietic Stem Cell Transplantation; HLA-A Antigens; HLA-A2 Antigen; Humans; In Vitro Techniques; Intensive care medicine; Male; Medical sciences; Middle Aged; Pilot Projects; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; T-Lymphocytes - immunology; Transplantation Chimera - immunology; Transplantation, Homologous; Tumors; Human; Immunopathology; Tumor associated antigen; Graft versus tumor reaction; Stem cell; Hematopoietic cell; Homograft; Graft versus host reaction; Non myeloablative treatment; Metastasis; Malignant tumor; Colonic disease; Carcinoembryonic antigen; In vivo; Colon cancer; Treatment; T-Lymphocyte; Digestive diseases; Graft; Intestinal disease; Advanced stage
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2005-10-3945

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.