Chimeric Antigen Receptor (CAR) T Cell Therapy For Solid Tumors

Introduction

CAR-T(uning) will assess the technical and commercial feasibility of an improved and broadly applicable chimeric antigen receptor T-cell (CAR-T) approach based on a novel implemented mechanism of action. There is an urgent need for more effective treatment strategies against cancer, which remains the leading cause of death worldwide.

Current Challenges in Cancer Treatment

Immuno-oncology regimens such as immune checkpoint blockade therapy (ICT) and CAR-T therapy have emerged as powerful tools in cancer treatment. However, in the majority of patients, these therapies fail to achieve a long-lasting response.

Limitations of Existing Therapies

1. Cost: They remain costly and applicable to a limited range of cancer types.
2. CAR-T Therapy Challenges: Specifically, CAR-T therapy faces two unresolved challenges:
   • Limited therapy persistence.
   • Tumor-induced immunosuppression.

Consequently, no CAR-T therapy against solid tumor cancers has reached the market.

Innovative Approach

Prof. Gottfried Baier has uncovered that inhibition of orphan nuclear receptor NR2F6, a downstream target of T cell antigen receptor signaling intermediate PKCθ, overcomes these shortcomings in a two-fold manner:

1. Increased therapy persistence to improve its long-lasting effects.
2. Reduced immunosuppression at the tumor site to improve immune response.

Technical Validation

Within this ERC PoC, we will first technically validate this approach using in vivo mouse and ex vivo patient-derived tumor models. We will focus on NSCLC as the first indication, as it is one of the most difficult-to-treat solid cancers with a high mortality rate and disease burden.

Commercial Feasibility

Subsequently, commercial feasibility will be determined by:

1. Verifying IP position and strategy.
2. Performing in-depth market and competitor analyses.
3. Consolidating these into a business plan to establish the best path to commercialization.

Expected Impact

Successful commercialization of CAR-T(uning) would reduce the socioeconomic burden of NSCLC, extending and improving patient lives, and enable the development of long-lasting, (cost-)effective CAR-T therapies applicable to a greater range of cancer types.