Building the Future of Immunotherapy

Why durable responses in solid tumors demand immune coordination

T cell engagers have redefined what’s possible in cancer treatment. In blood cancers, they’ve delivered rapid and meaningful responses. But in solid tumors, that success has been harder to sustain. The challenge isn’t a failure of immune cell engagement, it’s a failure of immune coordination.

T cell engagers work by linking CD3 on a T cell to a tumor-associated antigen, triggering targeted cell killing. This delivers a strong initial response. But these therapies typically provide only the first activation signal (TCR stimulation via CD3). What’s often missing are the second and third signals that are essential for sustaining and expanding a productive T cell response.

Signal 2 comes from co-stimulatory molecules like CD28, delivered by antigen-presenting cells such as dendritic cells.

Signal 3 involves cytokines like IL-15 or IL-12, which support T cell survival, proliferation, and differentiation.

Without these, CD8+ T cells often activate briefly, then rapidly exhaust, losing their abi…