Measuring Host-vs-CAR-T immune responses

CAR-T cells are an engineered T cell therapeutic in which a chimeric antigen receptor (CAR) (a foreign protein) is expressed on the surface of autologous T cells. This foreign CAR protein has the potential to elicit immune responses from the host immune system.
The immune response could be (a) humoral, resulting in the formation of Anti-CAR antibodies and/or (b) cellular, resulting in the development of cytotoxic T cells that are specific to the CAR-T cell. A host vs CAR-T response may result in (a) the neutralization of the CAR, rendering the CAR-T therapeutic ineffective (b) or result in the CAR-T cells being killed by a cytotoxic T cell response akin to a host vs graft response. This may manifest as lack of persistence of CAR-Ts and as loss of efficacy. There may be other reasons for loss of efficacy, and hence understanding if immunogenicity is the reason for loss of efficacy will be key in determining whether a second dose may be meaningful, the timing of this second dose, the impact of lymphodepletion on immunogenicity etc.