The Big Questions in Cancer Immunotherapy: Can Cell Therapy Succeed in Solid Tumors?

CAR-T cell therapy changed what seemed possible in cancer immunotherapy. In B-cell leukemias and lymphomas, and later in multiple myeloma, genetically engineered T cells produced deep and sometimes durable responses in patients whose cancers had progressed through multiple previous treatments. Translating the same principle to solid tumors has proved considerably more difficult.

The reason is not simply that solid tumors are more resistant to immunotherapy. Blood cancers and solid tumors present fundamentally different problems for engineered immune cells. In hematologic malignancies, highly useful lineage-associated targets such as CD19 and BCMA can be accessed relatively easily. In solid tumors, an ideal antigen is rarely expressed uniformly by malignant cells while remaining absent from essential normal tissues. T cells must also reach the tumor, penetrate its architecture, remain functional in a hostile metabolic environment and continue recognizing a cancer that can evolve under immune pressure.