IMPROVED METHOD FOR INCREASING THE NUMBER OF TUMOR-REACTIVE T-LYMPHOCYTES IN IMMUNOTHERAPY OF ONCOLOGIC PATIENTS

摘要

1. A method of increasing the number of tumor-reactive CD4 + T-helpers and / or CD8 + T-lymphocytes, the method comprising! i) the first phase of stimulation of tumor-reactive CD4 + T-helpers and / or CD8 + T-lymphocytes derived from the tumor antigen along with at least one substance having agonistic activity against the IL-2 receptor to increase the viability of tumor-reactive CD4 + T-helper cells and / or CD8 + T-lymphocytes; and! ii) a second phase of activation and growth of tumor-reactive CD4 + T-helpers and / or CD8 + T-lymphocytes, where the second phase ii) is initiated when a CD25 cell surface marker is suppressed on CD4 + T-helpers and / or CD8 + T-lymphocytes, where suppression is defined as the fact that 5% or less of the T-lymphocyte population expresses CD25, and where phase ii) is initiated by adding tumor derived antigen to the T-lymphocytes to activate tumor-reactive CD25-negative T-lymphocytes. ! 2. The method according to claim 1, in which the first phase i) is initiated by the addition of at least one substance having agonistic activity against the IL-2 receptor. ! 3. The method according to claim 2, in which the substance having agonistic activity against the IL-2 receptor is IL-2. ! 4. The method according to claim 1, wherein the antigen derived from the tumor is a denatured tumor homogenate. ! 5. The method according to claim 4, in which the antigen derived from the tumor is autologous. ! 6. The method according to claim 1, which further comprises adding to the T-lymphocytes antigen-presenting cells together with the antigen obtained from the tumor. ! 7. The method according to claim 6, in which the antigen-presenting cells are irradiated peripheral blood leukocytes containing the antigen-presenting