CAR T-cell therapy: An overview

An overview of CAR-T therapy

CAR-T therapy, a groundbreaking fusion of immunotherapy, gene therapy, and cellular therapy, offers hope in the battle against cancer and challenging diseases. Unlike traditional immunotherapies that focus on blocking tumour cell evasion mechanisms, CAR-T takes a proactive approach by genetically engineering T cells. These engineered T cells precisely target cancer cells, minimising harm to healthy tissues, and have demonstrated remarkable efficacy, particularly in blood cancers like leukaemia and lymphoma.

With two FDA-approved therapies and over 240 clinical trials underway, CAR-T continues to demonstrate its potential to revolutionise healthcare. This overview delves into the science behind CAR-T, the challenges it faces, and available tools to overcome them.

Understanding CAR-T and cytotoxicity

CAR-T therapies leverage Chimeric Antigen Receptors (CARs), synthetic receptors designed to recognise cancer antigens. The CAR is cloned and expressed in T cells, which are then tested to ensure CAR expression. Subsequently, the resulting CAR T cells are infused back into the patient to directly target antigen-expressing cancer cells.

Integrating intracellular signalling domains empowers CAR-T cells to activate, release cytokines, and exert cytotoxic effects on target cells. Notably, CAR-T bypasses the need for MHC/TCR activation, streamlining the immune response against cancer.

Despite its promise, CAR-T therapy can induce severe side effects, including cytokine release syndrome. Ongoing research focuses on enhancing safety profiles through the incorporation of additional signalling domains, such as CD28 or 4-1BB, regulating T cell expansion and persistence.

Advancements in signaling domains

Pivotal advancements in signalling domains have enhanced the effectiveness and safety of CAR-T therapy. Initially utilizing CD3 as the sole signalling domain, researchers have diversified and optimised signalling domains to improve CAR-T cell function, reduce toxicity, and broaden applicability.

Continued innovation includes third-generation enhancements with signalling domains like CD27, CD28, ICOS, and OX40, optimising CAR-T cell targeting. Costimulatory domains such as CD28 and ICOS provide secondary signalling cues, promoting T-cell activation, proliferation, and survival, demonstrating superior CAR-T cell expansion, persistence, and anti-tumour activity compared to CD3.

Characterising cancer antigens

The evaluation of CAR expression is pivotal for CAR-T production, facilitated by specialised cell lines expressing key cancer antigens. Beyond CD19, these cell lines encompass a spectrum of antigens crucial for assessing CAR-T specificity and efficacy. Cancer cells express diverse antigens, including tumour-specific and tumour-associated antigens, whose expression levels and dynamics influence disease progression and treatment outcomes.

Always ensure your engineered cell lines of choice are highly-validated for accurate research - such as those from cell line experts, BPS Bioscience.

Expanding applications 

CAR-T therapy is evolving beyond blood cancers, with ongoing research exploring its potential in treating solid tumours and other malignancies. Its adaptability to target various tumour antigens and its ability to induce durable responses make it a promising candidate for diverse cancer types. Combined with checkpoint inhibitors or traditional chemotherapy, CAR-T therapy becomes a vital component in multimodal cancer therapy approaches.

Beyond cancer, engineered T cells offer potential applications in chronic inflammatory conditions and organ transplantation, presenting transformative solutions for diverse medical challenges.

Useful tools for CAR-T therapy research

BPS Bioscience, recognised cell line engineering experts, offer unique products for CAR-T research, including TCR, B2M, and CIITA knockout cell lines. Additionally, they provide cell lines expressing common CAR targets, often with luciferase reporters for monitoring, and biotin-labelled antigens recognised by CAR-T cells for improved detection and validation through flow cytometry.

For personalised assistance with your specific research needs, contact the cell line specialists at Cambridge Bioscience.