Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy

CAR‐T‐cell products in solid tumors: Progress, challenges, and strategies

“…Moreover, this technology can be utilized to screen for potential new targets for intractable diseases by analyzing dynamic changes in T-cell populations and retrieving CAR information from amplified effector cell populations. 43…”

“…For example, as mentioned above, the synthetic CAR libraries with 10 6 diversity can be displayed on multiple immune cells, CAR T cells with rich antigen correspondence can be applied for both treatment and target-screening. 43 Similarly, evaluated in pooled assays during repetitive stimulation that mimics persistent tumor antigen exposure, "CAR pooling" comprising 40 CARs with both inhibitory and stimulatory signaling domains derived from various innate and adaptive immune cells were engineered to screen CAR-T cell subsets with critical T cell effector functions. 215 The potential of this platform is to be expanded to test receptor combinations with larger storage capacity, which may cover novel and surprising CARs.…”

“…The synthetic CAR libraries have been displayed on human NK‐92 cells, which exhibit universal targeting properties and eradicated established tumors in xenograft models. Moreover, this technology can be utilized to screen for potential new targets for intractable diseases by analyzing dynamic changes in T‐cell populations and retrieving CAR information from amplified effector cell populations 43 …”

“…Such consideration is based on the complex genomic and phenotypic changes of tumors under therapeutic stress, as well as consequent shifts in numerous conditions available for effective treatment. For example, as mentioned above, the synthetic CAR libraries with 10 6 diversity can be displayed on multiple immune cells, CAR T cells with rich antigen correspondence can be applied for both treatment and target‐screening 43 . Similarly, evaluated in pooled assays during repetitive stimulation that mimics persistent tumor antigen exposure, “CAR pooling” comprising 40 CARs with both inhibitory and stimulatory signaling domains derived from various innate and adaptive immune cells were engineered to screen CAR‐T cell subsets with critical T cell effector functions 215 .…”

Challenges and new technologies in adoptive cell therapy

“…They discovered that this library could recognize non-self-antigens and exhibit antigen-dependent clonal expansion, resulting in an increased population of tumor-specific effector cells and long-lasting anti-tumor responses. Moreover, the synthetic library led to robust immunological memory and the recognition of mutated or evolved tumors owing to the maintenance of CAR diversity [ 196 ]. Similar to TIL therapy, this design has advantages in that it can target multiple antigens and thus overcome the issue of heterogeneity.…”