Patients with non-curable disseminated follicular lymphoma receive local radiotherapy targeting single lymph nodes and injection of low-dose rituximab (anti-CD20) and autologous dendritic cells. The therapy is repeated 3 times, targeting different lesion. Aims are to induce tumor immunity and clinical responses.

The clinical protocol is based on the rationale that the immune system has been developed to combat infectious disease. To mimic the environment in infected tissue, selected tumor-affected lymph nodes are treated locally with a single dose of 8 Gy radiotherapy and injected with therapeutic antibody (anti-CD20/Rituximab). Later, dendritic cells (DC) are injected into the damaged tumor tissue together with a stimulatory cytokine (GM-CSF) to initiate an immune response. Patients with untreated or relapsed stage III/IV follicular lymphoma not in need of standard therapy receive intra-tumoral injections of low-dose anti-CD20 antibodies (5 mg) on days 1 and 3 and local radiotherapy on day 2. On days 4 and 5, dendritic cells generated from monocytes isolated from the patients blood are injected into the site together with the stimulatory cytokine GM-CSF administered subcutaneously. Additional lymph nodes are treated similarly after 2 and 4 weeks. The treatment is thus performed three times, targeting different lymphoma nodes. The primary aims are to induce tumor-specific immune responses and clinical responses.

Inclusion Criteria:

1. Age 18 years and older
2. Histologically confirmed (by WHO classification) untreated and relapsed indolent non-Hodgkin's B-cell lymphoma of low-grade follicular, marginal zone, lymphoplasmocytic or small lymphocytic subtypes.
3. Stage III/IV
4. Adequate bone marrow function (leukocyte count>2,0, neutrophil count>1.0, platelets>50)
5. Two or more separate lymph nodes > 1,5 cm available for biopsy or treatment.
6. Measurable disease present other than biopsy site and injection site(s).
7. Required wash-out period after previous treatment: Chemotherapy - 8 weeks, Radiotherapy - 4 weeks, Rituximab - 12 weeks
8. WHO status 0-1
9. Life expectancy of more than 6 months
10. Written informed consent
11. Able to comply with the treatment protocol -

Exclusion Criteria:

1. Patients with progressive lymphoma in need of systemic therapy or standard dose irradiation.
2. Chronic bacterial, viral or fungal infection
3. Pre-existing autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
4. Known history of HIV
5. Central nervous system involvement of lymphoma
6. Current anticoagulant therapy which can not safely be paused during treatment injections (ASA < 325 mg/day allowed)
7. Pregnancy -