PMID- 16403911 OWN - NLM STAT- MEDLINE DCOM- 20060524 LR - 20210206 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 107 IP - 9 DP - 2006 May 1 TI - 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. PG - 3795-803 AB - 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. FAU - Carnevale-Schianca, Fabrizio AU - Carnevale-Schianca F AD - Laboratory of Tumor Immunology, Division of Medical Oncology, Unit of Radiation Therapy, Institute for Cancer Research and Treatment, IRCC, Strada Provinciale No. 140, Candiolo, Turin, Italy. FAU - Cignetti, Alessandro AU - Cignetti A FAU - Capaldi, Antonio AU - Capaldi A FAU - Vitaggio, Katiuscia AU - Vitaggio K FAU - Vallario, Antonella AU - Vallario A FAU - Ricchiardi, Alberto AU - Ricchiardi A FAU - Sperti, Elisa AU - Sperti E FAU - Ferraris, Renato AU - Ferraris R FAU - Gatti, Marco AU - Gatti M FAU - Grignani, Giovanni AU - Grignani G FAU - Rota-Scalabrini, Delia AU - Rota-Scalabrini D FAU - Geuna, Massimo AU - Geuna M FAU - Fizzotti, Marco AU - Fizzotti M FAU - Sangiolo, Dario AU - Sangiolo D FAU - Sottile, Antonino AU - Sottile A FAU - De Rosa, Giovanni AU - De Rosa G FAU - Bucci, Anna Rosa AU - Bucci AR FAU - Lambertenghi-Deliliers, Giorgio AU - Lambertenghi-Deliliers G FAU - Benedetti, Edoardo AU - Benedetti E FAU - Nash, Richard AU - Nash R FAU - Aglietta, Massimo AU - Aglietta M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060110 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Carcinoembryonic Antigen) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) SB - IM MH - Adult MH - Aged MH - Carcinoembryonic Antigen MH - Case-Control Studies MH - Colonic Neoplasms/immunology/secondary/*therapy MH - Female MH - Graft vs Host Disease/immunology MH - Graft vs Tumor Effect/immunology MH - HLA-A Antigens MH - HLA-A2 Antigen MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - In Vitro Techniques MH - Male MH - Middle Aged MH - Pilot Projects MH - T-Lymphocytes/immunology MH - Transplantation Chimera/immunology MH - Transplantation, Homologous EDAT- 2006/01/13 09:00 MHDA- 2006/05/25 09:00 CRDT- 2006/01/13 09:00 PHST- 2006/01/13 09:00 [pubmed] PHST- 2006/05/25 09:00 [medline] PHST- 2006/01/13 09:00 [entrez] AID - S0006-4971(20)65570-7 [pii] AID - 10.1182/blood-2005-10-3945 [doi] PST - ppublish SO - Blood. 2006 May 1;107(9):3795-803. doi: 10.1182/blood-2005-10-3945. Epub 2006 Jan 10.