In recent years, the groundbreaking success of CAR T-cell therapies in treating hard-to-treat blood cancers has been a beacon of hope. However, translating this success to solid tumors, which constitute the majority of cancer cases, has proven challenging. Encouragingly, recent trial results, such as those from BioNTech’s BNT211, suggest that researchers are making strides in developing next-generation CAR T therapies for solid tumors.

Overcoming Solid Tumor Challenges: Traditionally, CAR T therapies have excelled in blood cancers, leveraging engineered T cells to utilize the patient’s immune system. Solid tumors present unique challenges, including finding the right protein to target without harming healthy tissues. BioNTech’s approach, targeting Claudin-6, a protein present in fetal tissue and certain cancers but absent in healthy adult tissue, has shown promise in mitigating this challenge.

Enhancing Precision with “Logic Gates”: To address the complexity of solid tumors, researchers are exploring the incorporation of “logic gates” into CAR T cells. By engineering T cells with multiple receptors, these cells can activate based on specific conditions, mimicking biological logic. This approach allows for a more nuanced response, akin to the natural functioning of T cells, with potential applications in ovarian cancer therapies, as seen in Arsenal Bio’s clinical trial.

Innovative Targeting Strategies: In cases where unique proteins for targeting aren’t readily available, researchers are exploring alternative strategies. A study from Columbia University introduces the concept of using engineered bacteria to tag tumors, providing a distinctive target for CAR T cells. While not yet ready for clinical trials, this approach opens new possibilities for cancer treatment.

Balancing Potency and Safety: The challenge lies in striking a balance between the potency of CAR T therapies and potential toxicity. Cytokine release syndrome, a known side effect, emphasizes the delicate equilibrium needed for effective yet safe treatments. Switchable CAR T therapies, requiring an antibody for activation, provide a natural “off” switch, offering control over T cell activity and reducing adverse effects.

Addressing Durability Concerns: Durability remains a concern, with CAR T cells sometimes failing to persist long enough for complete cancer eradication. BioNTech’s innovative approach involves combining CAR T cells with an mRNA vaccine, aiming to enhance their longevity. Preliminary results indicate improved staying power, emphasizing the potential of this strategy.

The Road Ahead: As hundreds of CAR T therapies undergo clinical trials, researchers remain optimistic about finding effective formulas for treating solid tumors. Lessons learned from trials, even those without immediate success, contribute to the evolving landscape of cancer treatment.

The progress showcased in recent trials, particularly BioNTech’s BNT211, underscores the evolving landscape of CAR T therapies, offering renewed hope for effective treatments against solid tumors.

By Impact Lab