Antigen-Specific Lymphocyte Expansion Using Neo-Antigen Peptide Pools

The patent applies preliminary action by incorporating peptide pools comprising neo-antigens into the initial TIL culture setup before expansion begins. This pre-stimulation ensures that neo-antigen-specific T cell clones are selectively activated and enriched from the outset, rather than attempting to isolate and expand them separately afterward. The peptide pools are added to the culture medium or presented by APCs during the initial culture phase, enabling specific T cells to proliferate preferentially while maintaining overall TIL quantity.

The patent applies universality by using peptide pools that can be presented by multiple types of antigen-presenting cells (APCs), including dendritic cells, B cells, and macrophages. These APCs can be generated from the patient's own tumor samples or normal tissues, making the system adaptable to different patient contexts. The peptide pools are designed to cover multiple neo-antigens simultaneously, allowing a single culture system to enrich for multiple antigen-specific T cell clones rather than requiring separate cultures for each antigen.

The patent applies preliminary action by performing thymic selection bias correction during the initial culture phase before bulk expansion occurs. Peptide pools comprising neo-antigens are introduced to stimulate and select for T cell clones with high affinity for these antigens. This early selection ensures that only T cells with appropriate specificity and functionality are allowed to proliferate in subsequent expansion phases, preventing the counter-selection that would occur if expansion happened without prior peptide stimulation.