#1 Lack of ideal solid cancer antigen targets

The current CAR-T market is driven largely by CAR-T cells targeted against blood cancers and at only one antigen (CD19).

Anti-CD19 CAR-T cells have consistently demonstrated high anti-tumour efficacy in children and adults affected by relapsed B-ALL, chronic lymphocytic leukemia and B cell non-Hodgkin lymphoma, with complete remissions ranging from 70 to 94% across several trials1.

CD19 is the target antigen for the only two FDA-approved CAR-T therapies (Kymirah and Yescarta, both approved in 2017).

However, CD19 is only present on B cells and no other cells, so a CAR-T expressing a CD19 CAR is only useful against malignancies of B cells.

Like CD19, other leading solid tumour antigens (HER2, GD2, GPC3 and mesothelin) are …
* limited to expression on one or a small number of cancers
* are also expressed on healthy cells

In solid cancer clinical trials, there has been little positive data for most of the antigens studied (an exception is GD2 for neuroblastoma where a complete response rate of 50% was recorded).

The vast majority of antigens targeted in clinical trials so far have not been specific for solid cancer cells, but rather tumour-associated antigens (TAAs) that are overexpressed on tumour cells but also still present on healthy cells. Significant on-target off-tumour effects have been recorded where the CAR-Ts have attacked both diseased and healthy cells.

2018-09-10T11:54:56+09:30