title: 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.
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.
authors.affiliation: 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.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carnevale-Schianca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cignetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Capaldi
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Vitaggio
authors.forename: Antonella
authors.initials: A
authors.lastname: Vallario
authors.forename: Alberto
authors.initials: A
authors.lastname: Ricchiardi
authors.forename: Elisa
authors.initials: E
authors.lastname: Sperti
authors.forename: Renato
authors.initials: R
authors.lastname: Ferraris
authors.forename: Marco
authors.initials: M
authors.lastname: Gatti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grignani
authors.forename: Delia
authors.initials: D
authors.lastname: Rota-Scalabrini
authors.forename: Massimo
authors.initials: M
authors.lastname: Geuna
authors.forename: Marco
authors.initials: M
authors.lastname: Fizzotti
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
authors.forename: Antonino
authors.initials: A
authors.lastname: Sottile
authors.forename: Giovanni
authors.initials: G
authors.lastname: De Rosa
authors.forename: Anna Rosa
authors.initials: AR
authors.lastname: Bucci
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
authors.forename: Edoardo
authors.initials: E
authors.lastname: Benedetti
authors.forename: Richard
authors.initials: R
authors.lastname: Nash
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
mesh_terms: D000328:Adult; D000368:Aged; D002272:Carcinoembryonic Antigen; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D002272:Carcinoembryonic Antigen; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen