title: Sequential intranodal immunotherapy induces antitumor immunity and correlated regression of disseminated follicular lymphoma.
abstract: Advanced stage follicular lymphoma (FL) is incurable by conventional therapies. In the present pilot clinical trial, we explored the efficacy and immunogenicity of a novel in situ immunotherapeutic strategy. Fourteen patients with untreated or relapsed stage III/IV FL were included and received local radiotherapy to solitary lymphoma nodes and intranodal injections of low-dose rituximab (5 mg), immature autologous dendritic cells, and granulocyte-macrophage colony-stimulating factor at the same site. The treatment was repeated 3 times targeting different lymphoma nodes. Primary end points were clinical responses and induction of systemic immunity. Five out of 14 patients (36%) displayed objective clinical responses, including 1 patient with cutaneous FL who showed regression of skin lesions. Two of the patients had durable complete remissions. Notably, the magnitude of vaccination-induced systemic CD8 T-cell-mediated responses correlated closely with reduction in total tumor area (r = 0.71, P = .006), and immune responders showed prolonged time to next treatment. Clinical responders did not have a lower tumor burden than nonresponders pretreatment, suggesting that the T cells could eliminate large tumor masses once immune responses were induced. In conclusion, the combined use of 3 treatment modalities, and in situ administration in single lymphoma nodes, mediated systemic T-cell immunity accompanied by regression of disseminated FL. The trial was registered at www.clinicaltrials.gov as #NCT01926639.
authors.affiliation: Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway; K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway;
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Kumari
authors.affiliation: K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Walczak
authors.affiliation: Department of Radiology.
authors.forename: Ulf
authors.initials: U
authors.lastname: Madsbu
authors.affiliation: Department of Radiology.
authors.forename: Trond
authors.initials: T
authors.lastname: Hagtvedt
authors.affiliation: Department of Nuclear Medicine.
authors.forename: Trond Velde
authors.initials: TV
authors.lastname: Bogsrud
authors.affiliation: Department of Cellular Therapies, and.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kvalheim
authors.affiliation: Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway;
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.affiliation: Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway;
authors.forename: Ellen
authors.initials: E
authors.lastname: Aurlien
authors.affiliation: Department of Pathology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.affiliation: Department of Pathology, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Tierens
authors.affiliation: K. G. Jebsen Center for Cancer Immunotherapy, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology.
authors.forename: Johanna
authors.initials: J
authors.lastname: Olweus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D019496:Cancer Vaccines / Q000627:therapeutic use; D003713:Dendritic Cells / Q000187:drug effects; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008198:Lymph Nodes / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000628:therapy*; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D012878:Skin Neoplasms / Q000628:therapy; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines; D000069283:Rituximab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor