rWTC‐MBTA Vaccine, Alone and Enhanced with Anti‐PD1, Elicits Immune Responses against CNS and Peripheral B‐Cell Lymphoma

Central nervous system (CNS) lymphomas are difficult to treat due to their aggressive nature, limited brain accessibility, and poor response to conventional therapies. This study evaluates the rWTC‐MBTA vaccine, alone or with anti‐PD1 therapy, in A20 B‐cell lymphoma models. The vaccine alone significantly inhibits tumor growth and extends survival in both subcutaneous and intracranial settings by triggering strong innate and adaptive immune responses, including long‐term memory. Immune profiling reveals dynamic responses in lymph nodes and tumor‐infiltrating lymphocytes over time. Co‐culture assays with lymph node or spleen cells from vaccinated mice show enhanced tumor cell killing and increased IFN‐γ and TNF‐α levels, indicating lymphoma‐specific immunity. In the intracranial model, control mice has dense tumor infiltration in the brain, while vaccinated mice exhibit more dispersed tumors with reduced spread to ventricles and meninges. Vaccination also shifts the tumor microenvironment toward a more active antitumor state, marked by increased PD‐1⁺ CD8⁺ T cells. Combining the vaccine with anti‐PD1 further enhances antitumor effects. These findings demonstrate that rWTC‐MBTA induces potent and durable immune responses against CNS and peripheral lymphomas, offering long‐term protection and showing synergistic benefit when combined with immune checkpoint blockade.