Oncology immunotherapy mechanisms and efficacy

Define a bispecific antibody and contrast its structure and function with a standard monoclonal antibody.

Explain the mechanism of a T-cell engaging bispecific antibody (e.g., a BiTE like blinatumomab), detailing how it cross-links a T-cell to a tumor cell.

Identify the key binding targets for a T-cell engaging bispecific, specifying CD3 on the T-cell and a tumor-associated antigen (TAA) on the cancer cell.

Describe the modular structure of a Chimeric Antigen Receptor (CAR), identifying its antigen-binding (scFv), transmembrane, and intracellular signaling domains.

Explain how a CAR-T cell recognizes and kills a tumor cell, contrasting its MHC-independent mechanism with that of a normal T-cell.

Compare the functional impact of different co-stimulatory domains (e.g., CD28 vs. 4-1BB) on CAR-T cell persistence and effector function.

Outline the key steps in manufacturing autologous CAR-T cells, from patient apheresis to gene transfer and re-infusion.

Describe the biological basis of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) as key toxicities of T-cell engaging therapies.