title: Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer-A phase I-II study.
abstract: Dendritic cell-based active immunotherapies of cancer patients are aimed to provoke the proliferation and differentiation of tumor-specific CD4(+) and CD8(+) T-lymphocytes towards protective effector cells. Isolation and in vitro differentiation of circulating blood monocytes has been established a reasonable platform for adoptively transferred DC-based immunotherapies. In the present study the safety and tolerability of vaccination by autologous tumor cell lysates (oncolysate)- or carcinoembriogenic antigen (CEA)-loaded DCs in patients with colorectal cancer was investigated in a phase I-II trial. The study included 12 patients with histologically confirmed colorectal cancer (Dukes B2-C stages). Six of the patients received oncolysate-pulsed, whereas the other six received recombinant CEA-loaded autologous DCs. The potential of the tumor antigen-loaded DCs to provoke the patient's immune system was studied both in vivo and in vitro. The clinical outcome of the therapy evaluated after 7 years revealed that none of the six patients treated with oncolysate-loaded DCs showed relapse of colorectal cancer, whereas three out of the six patients treated with CEA-loaded DCs died because of tumor relapse. Immunization with both the oncolysate- and the CEA-loaded autologous DCs induced measurable immune responses, which could be detected in vivo by cutaneous reactions and in vitro by lymphocyte proliferation assay. Our results show that vaccination by autologous DCs loaded with autologous oncolysates containing various tumor antigens represents a well tolerated therapeutic modality in patients with colorectal cancer without any detectable adverse effects. Demonstration of the efficacy of such therapy needs further studies with increased number of patients.
authors.affiliation: Clinical Centre for Cell Therapy, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Hunyadi
authors.forename: Csilla
authors.initials: C
authors.lastname: András
authors.forename: Imre
authors.initials: I
authors.lastname: Szabó
authors.forename: János
authors.initials: J
authors.lastname: Szántó
authors.forename: Kornélia
authors.initials: K
authors.lastname: Szluha
authors.forename: Sándor
authors.initials: S
authors.lastname: Sipka
authors.forename: Péter
authors.initials: P
authors.lastname: Kovács
authors.forename: Attila
authors.initials: A
authors.lastname: Kiss
authors.forename: Gyula
authors.initials: G
authors.lastname: Szegedi
authors.forename: István
authors.initials: I
authors.lastname: Altorjay
authors.forename: Péter
authors.initials: P
authors.lastname: Sápy
authors.forename: Péter
authors.initials: P
authors.lastname: Antal-Szalmás
authors.forename: László
authors.initials: L
authors.lastname: Tóth
authors.forename: György
authors.initials: G
authors.lastname: Fazekas
authors.forename: Éva
authors.initials: É
authors.lastname: Rajnavölgyi
mesh_terms: D000293:Adolescent; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D002272:Carcinoembryonic Antigen