Immunotherapy Strategies in Follicular Lymphoma: Antibodies, Vaccines and Cells

Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Therapeutic strategies vary from withholding treatment to aggressive chemoimmunotherapy regimes, and stem cell transplantation, depending on the stage and risk stratification at diagnosis. A prominent role of the microenvironment in FLcell survival and lymphomagenesis has been brought to light and consequently the manipulation of the FL-cell niche is progressively becoming an important therapeutic tool in FL. Chemotherapy agents are no longer under the spotlight, leaving the main role to immunotherapeutic strategies and targeted therapy that aim towards disease control with minimal side-effects and sequelae. Immunotherapy with monoclonal antibodies, radioimmunotherapy and vaccines, has resulted in increased response rates and survival in FL patients.

Adoptive immunotherapy is an emerging strategy for FL treatment, aiming to exploit the immune system's natural tendency to attack tumoral cells. AntiCD20 monoclonal antibodies have become the backbone of first line and relapse treatments combined with chemotherapy regimens. Anti-idiotype vaccines are the best developed active immunotherapy strategy, with proven efficacy in patients with FL on first relapse. The other vaccine types (Dentritic cells, proteoliposomal or DNA) are still in preclinical development. Adoptive cell transfer (NK cells, LAK and effector T-lymphocytes), chimeric-antigen receptor (CAR) engineered T-cells and Bi-specific T-cell engaging antibodies (BiTE) for passive immunotherapy remain also experimental approaches, although promising pre-clinical results have recently become available.

The following chapter will summarize FL biology and conventional treatment with immunochemotherapy, with a final section focusing specifically on novel immunotherapy strategies (active and passive) for the treatment of FL.

Keywords: Adoptive cell-therapy, Anti-idiotype vaccines, Dentritic-cell vaccines, Follicular lymphoma, Immunotherapy, LAK cells, Monoclonal antibodies, NK cells, Radioimmunotherapy, Vaccines.