A Phase I/II Study of IPH1101 (BrHPP), Specific Agonist of Vã9Vä2 T Lymphocytes, in Combination with Rituximab Re-Treatment in Patients with Follicular Lymphoma. Interim Phase I Data.

Background: Unconventional γδ T lymphocytes are innate immunity effectors bearing very strong anti-tumoral activity. Previous studies have documented that malignant B cells are highly sensitive to γδ T cells mediated cellular toxicity. IPH1101 is a chemically-synthesized, specific antigen for γδ T cells: IPH1101 triggers the synthesis of pro-inflammatory cytokines by γδ T cells - inducing the recruitment of other cell effectors and facilitating implementation of an adaptive response - and potentiates the direct cytotoxic activity of γδ T cells against a large number of tumor B-cell lines. Also, IPH1101-activation of γδ T cells in the presence of low doses of IL-2 leads to their proliferation and differentiation into effectors capable of mediating ADCC. ADCC is the main known molecular mechanism underlying rituximab bioactivity. Increasing the number and the activation of killer lymphocytes mediating ADCC is crucial for therapeutic potency and deserves to be tested in a clinical trial. The purpose of this study is to assess the clinical efficacy, the biological activity, and the safety of the association of IPH1101 with low doses of IL-2, combined to a standard rituximab re-treatment, in patients with Follicular Lymphoma.