Currus Biologics is developing a platform technology to improve the efficacy of CAR- T cell therapies in solid tumour cancers
The clinical utility of CAR-T cell therapies is limited in all common solid tumours, such as cancers of the breast, colon, pancreas and prostate.
Clinical and preclinical studies of CAR-T cells have identified multiple roadblocks when targeted towards solid tumours, including:
a limited array of targetable antigens, heterogeneous antigen expression and antigen loss;
limited T cell fitness and survival including proliferation and persistence before reaching tumour sites;
an inability of T cells to efficiently traffic to tumour sites and penetrate physical barriers; and
an immunosuppressive tumour microenvironment.
Immune check point antibody blockade has demonstrated that cytotoxic T cells can be appropriately activated to target advanced solid tumours.
Currus Biologics uses a novel and differentiated approach to improve the efficacy of CAR-T cell or T cell receptor (TCR) therapy in solid tumour indications.
Currus Biologics’ approach uses a bi-specific antibody, which recognises and simultaneously binds markers on CAR-T or TCR cells and professional antigen presenting cells (APCs), enabling their interaction.
The Bispecific Engagers of Antigen Presenting Cells and T cells (BEATs) enables the CAR-T or TCR cells to engage with professional antigen presenting cells (APCs) in the lymph nodes, away from the suppressive tumour microenvironment.
With the BEAT engaging the professional antigen presenting cells (APCs) and the CAR-T or TCR cell therapy simultaneously, the CAR-T or TCR cells proliferate and expand in a supportive natural environment. The CAR-T or TCR cells gain the appropriate licensing and then egress from lymphoid tissues to effect the potent targeting of solid tumours.
In several models of solid tumours, the combination of the BEAT concept and CAR-T cell therapy has demonstrated strong CAR-T cell proliferation and persistence with CAR-T cell trafficking to, and infiltration of, large and established solid tumours.
Importantly, the BEAT drives potent CAR-T cell mediated anti-tumour efficacy and supports the generation of endogenous immunological responses that extends to additional antigens.
The BEAT technology can be used with either CAR-T or TCR cell therapy to overcome the roadblocks seen with the treatment of solid tumours.