Driving CAR-Ts for Treatment in Cancer and Immunology

Pooja Goyal

Chimeric Antigen Receptor (CAR) T-cell therapies constitute a significant and growing segment within the cell therapy space. Specifically, CAR T-cell therapy involves genetically modifying T-cells to express chimeric antigen receptors, which target tumor antigens.

This personalized approach to cancer treatment has shown noteworthy effectiveness, particularly in treating relapsed or refractory liquid tumors like acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), when more conventional therapies have not been successful. Lifileucel, a non-genetically modified tumor-infiltrating lymphocyte (TIL) therapy, recently gained approval for solid tumors. Extensive research in the field has given a boost to the number of clinical trials in cell therapies.

CD19, BCMA, and CD22 are well-established targets in CAR-T cell therapy. These antigens play a crucial role in directing the immune response against cancer cells. However, it’s exciting to see emerging interest in other targets like CD7, HER2 (Human Epidermal Growth Factor Receptor 2), and NKG2D (Natural Killer Group 2D). These novel targets expand the therapeutic landscape, offering hope for improved outcomes in cancer treatment.

Carving a route in immunology

Excitingly, CAR-T therapies are now not just restricted to cancer but have pivoted to immunology as well by showing promising activity in a number of autoimmune disorders, such as systemic lupus erythematosus (SLE) and lupus nephritis (LN).

The recent European Alliance of Associations for Rheumatology (EULAR) 2024 conference highlighted CAR T-cell modalities in autoimmune diseases. Early-phase clinical trials demonstrated encouraging results with CAR T-cell therapies, due to their effect on the auto-immune responses of the immune system that may help achieve drug-free remission for patients with SLE and LN.

However, the rosy picture comes with a dent from the fact that there have been studies (both academic and industry sponsored) where patients relapsed after being in remission with CAR-T therapy. Considering the mixed efficacy reviews, researchers are closely monitoring the cases in clinical trials to better understand the long-term efficacy with CAR-T therapies in the autoimmune disease sector.

Challenges in uptake

Despite the promising efficacy, in real world, the adoption of CAR-T cell therapies faces several challenges, including their cost, manufacturing, and availability of adequate capacity in treatment centers for administration, especially for cancer patients. Their personalized nature (as the therapy is tailored to target the disease condition of each specific patient) and the challenge of manufacturing with consistent quality, scalability, and safety, significantly contributes to the cost. The need for specialized medical centers with the infrastructure to administer cell therapies further limits the access to these therapies.

Moving toward a brighter future

Nonetheless, efforts are ongoing to address these challenges, including research into more cost-effective manufacturing methods, improving logistics, and expanding treatment centers. As the field evolves, we hope to see increased accessibility and affordability for patients in need. Continuous innovations in the bioprocessing industry are focusing on scalability and efficiency to overcome these.Beyond CAR-T, other cell therapy modalities are evolving, including NK cell therapy, dendritic cell therapy, stem cell therapy, and myeloid-derived cell therapy. Research is also being focused on allogeneic therapies which are derived from healthy donor cells, thus offering “off-the-shelf” availability and faster access to patients.

Overall, exciting advancements continue to unfold in this transformative and evolving field, making it critical for biopharma companies to stay ahead of the curve by keeping themselves informed of the clinical and commercial developments in the cell therapy space.

About the Author

Pooja Goyal is a senior consultant with Lifescience Dynamics.