Xyphos is developing treatments for relapsed hematological malignancies and solid tumors using our flexible and controllable CAR-T cell therapy platform called ACCEL™ (Advanced Cellular Control through Engineered Ligands). ACCEL enables precise control of activity and targeting of our universal CAR-T cell, termed convertibleCAR-T™, using any tumor-specific full antibody and can add critical functionality to convertibleCAR-T cells.
The recent progress in the field of immuno-oncology has dramatically changed the clinical approach to treating cancer. Tremendous excitement centers on Adoptive Cell Therapy (ACT), an approach that delivers living cells derived from the human immune system and engineered to target and kill cancer cells. Results from numerous clinical studies of pioneer CAR-T therapy products showed tremendous success and provided evidence of complete and durable cancer remissions. However, at the same time, many challenges to effect safe and effective CAR-T therapy became evident.
Building on the success of the pioneer CAR-T therapies, Xyphos is developing best-in-class CAR-T therapy products based on our ACCEL technology which includes our universal convertibleCAR and a family of bispecific, antibody-like adaptor molecules, called MicAbodies™ and MicAdaptors. Our vision is to provide precision, control, safety and ultimately durable efficacy to this revolutionary class of cancer therapy.
Comparison of Pioneer CAR-T and Xyphos’ ACCEL Technologies:
Challenges of pioneer CAR-T technology:
Significant problems that stem from pioneer CAR-T technology:
- Lack of dose control of CAR-T cell activity
- Uncontrollable on-target off-tumor toxicity
- Single antigen targeting
- Non-human tumor binding domains
- Inability to control CAR-T cell persistence
- Inability to provide immune checkpoint control
- No control of cell activity in “emergency” situations
- Lack of non-invasive in vivo biomarkers
ACCEL technology provides the solution
Our approach uniquely solves frequent CAR-T problems:
- Dose control of convertibleCAR-T cell activity
- MicAbody PK controls on-target off tumor toxicity
- Ability to switch and multiplex targeting
- Human derived components
- Modulation of convertibleCAR-T cell function to better adept treatment
ACCEL is based on a unique receptor-ligand control system engineered from protein components of the human NKG2D receptor/MIC ligand immune surveillance pathway. Through minimal engineering of the natural NKG2D receptor and directed evolution of small modular MIC domains that selectively bind the mutated NKG2D, we created an inert NKG2D CAR (iNKG2D CAR) that can only be activated using bispecific MIC-Antibody fusions (MicAbodies). The resulting platform enables a single iNKG2D CAR-T cell therapy to be precisely controlled using a tumor specific MicAbody and redirected to any antigen of choice. Further, using bispecific MIC-effector fusions (MicAdaptors), we can add critical functionality (e.g. cytokine stimulation, checkpoint blockade, cell ablation, imaging biomarkers) specifically to our convertibleCAR-T cells.
We have demonstrated in vitro and in vivo proof-of-concept with impressive results with multiple convertibleCAR-T and MicAbody combinations showing precise targeting and dose-dependent control of the convertibleCAR-T system.