Global Tcr Therapy Market Pipeline

Global Tcr Therapy Market Pipeline

TCR therapy, or T-cell receptor therapy, is an innovative form of immunotherapy that leverages the body’s own immune system to combat cancer. This approach involves extracting a patient’s T-cells and genetically engineering them to express receptors specifically designed to recognize and bind to cancer-associated antigens presented by the major histocompatibility complex (MHC) on tumor cells.

Unlike CAR-T therapy, which targets antigens on the cell surface, TCR therapy can target intracellular proteins, allowing for a broader range of cancer targets. Once engineered, these T-cells are expanded in the laboratory and reinfused into the patient, where they seek out and destroy cancer cells. TCR therapy holds significant promise for treating various cancers, including solid tumors, and is currently the focus of extensive research to optimize its efficacy and safety.

MARKET INSIGHTS

Key enablers of the global TCR therapy market growth:
• Growing number of promising clinical and preclinical studies
• Rising cancer incidence rates

According to the American Cancer Society, the United States is projected to see 1,958,310 new cancer cases and 609,820 cancer deaths in 2023. The rising incidence of cancer underscores the urgent need for more effective treatments, propelling TCR (T-cell receptor) therapy into the forefront. As cancer rates surge globally, the demand for innovative therapies like TCR, which harnesses the immune system to target cancer cells, is increasing.

With more patients being diagnosed with various forms of cancer, the market for TCR therapy naturally expands to address these diverse indications. This trend showcases the versatility of TCR therapy and its potential to meet the evolving needs of cancer patients, positioning it as a significant player in the field of oncology.

As more patients require advanced therapeutic options, TCR therapy’s ability to specifically target cancer cells positions it as a promising solution. Its adaptability across different cancer types enhances its appeal, making TCR therapy a crucial component in the ongoing battle against cancer and a key factor in the future landscape of oncology treatments.
• Surge in innovation and research activities

Key growth restraining factors of the global TCR therapy market:
• Toxicity from cytokine storms in TCR therapy
• Off-target effects and safety concerns in TCR gene transfer
• Challenges in selecting the optimal target antigen

T-cell receptors (TCRs) can only recognize peptide-HLA complexes and are effective against cancer cells that have matching HLA alleles, necessitating appropriate HLA matching. This means that TCR-T-cells derived from non-Chinese individuals cannot be directly applied to Chinese patients. The screening process for identifying TCRs with the optimal affinity threshold is challenging, as high-affinity TCRs are needed to enhance immune responses.

Identifying TCRs with high affinity for antigens is crucial for effective immune responses, but the affinity must be carefully regulated. If TCR affinity exceeds physiological limits, it can result in injury to the T-cells.

The mechanism of antigen recognition by TCR-expressing T-cells is vital for T-cell immunity. T-cells must quantitatively respond to antigens presented by pathogens while remaining unresponsive to similar antigens on host tissues.

TCR Therapy | Overview
• Introduction
• Structural characteristics of the TCR
• TCR diversity in the pre-selection repertoire

The pre-selection repertoire of T-cell receptors (TCRs) is shaped by both genetic and epigenetic factors. According to the accessibility hypothesis, gene segments must be accessible to recombination machinery, involving processes such as subnuclear relocation, DNA methylation, chromatin remodeling, histone modification, and germline transcription.

Although the activation of the 3′ proximal region of antigen receptor loci is well understood, the mechanisms controlling the accessibility and activation of the 5′ V region remain unclear. Research has shown that V genes in the immunoglobulin heavy chain locus recombine at different frequencies even when they have equal accessibility, implying that similar biases might also be present in TCR loci.

Recent analyses reveal that the frequency of out-of-frame TCR-α sequences is affected by the usage of V and J segments, indicating a genetic influence. Additionally, recombination bias causes a notable overlap in the TCR-β chain repertoire among syngeneic mice before thymic selection, highlighting a predisposition in the TCR repertoire composition that is significantly shaped by V(D)J recombination.
• TCR diversity in the naive pool
• TCR diversity in health and disease
• TCR clonotypes as markers of disease
• The TCR complex

The TCR receptor complex is an octameric structure with three dimeric signaling modules: CD247 ζ/ζ, CD3δ/ε, and CD3γ/ε, and variable α and β chains. Ionizable residues in the transmembrane domains stabilize the complex, while signaling molecules are essential due to the TCR’s short cytoplasmic tail.

TCRs exhibit low affinity for peptide/MHC ligands (dissociation constants of 1-100 μM); but T-cells maintain high antigen specificity and sensitivity through the formation of TCR microclusters, enhancing antigen recognition via an avidity-based mechanism.

Antigen-experienced T-cells (effector and memory) show increased sensitivity and require fewer costimulatory signals and lower antigen concentrations compared to naive T-cells, achieved through functional avidity maturation without changes in affinity.
• TCR co-receptors
• Associated molecules of the TCR complex involved in T-cell activation
• T-cell receptor-engineered T-cells for cancer treatment: Current status and future directions
• Identification of TCR sequences
• Improving the function of TCR-engineered T-cells in tumor microenvironment

COMPETITIVE INSIGHTS

Major players in the global TCR therapy market:
• Adaptimmune
• Gilead Sciences
• Alaunos Therapeutics
• Triumvira Immunologics
• Takara Bio

Gilead Sciences, a biopharmaceutical company established in 1987 in Foster City, California, specializes in researching, developing, and marketing medicines for life-threatening diseases. With over 7,000 employees spread across offices on six continents, Gilead focuses on therapeutic areas such as HIV/AIDS, hepatitis B and C, influenza, COVID-19, liver diseases, hematology, and oncology. Some of their notable products include Biktarvy, Complera, Descovy, Emtriva, Genvoya, Odefsey, Stribild, and Sunlenca.

KITE-439, developed by Gilead Sciences, is a T lymphocyte replacement therapy. Preclinical studies have shown efficacy with MHC class I-restricted T-cell receptor (TCR)-engineered T-cells targeting the E7 protein on HPV16-positive tumor cells. The drug is currently in Phase II clinical trials for the treatment of both solid and hematological malignancies.

Frequently Asked Questions (FAQs):
• How does TCR therapy work?

A: TCR therapy works by extracting T-cells from a patient, genetically engineering them to express specific T-cell receptors (TCRs) that can recognize cancer-associated antigens, and then reinfusing these modified T-cells back into the patient. These engineered T-cells then target and kill cancer cells displaying the specific antigen.
• What are the risks and side effects of TCR therapy?

A: Common risks and side effects of TCR therapy include cytokine release syndrome (CRS), neurotoxicity, and potential off-target effects that might damage healthy tissues. These side effects necessitate careful monitoring and management during and after treatment.
• How is TCR therapy different from CAR-T therapy?

A: While both TCR and CAR-T therapies involve genetically modifying T-cells, they differ in their target recognition mechanisms. CAR-T-cells recognize surface antigens on cancer cells through chimeric antigen receptors, whereas TCR therapy targets intracellular antigens presented by MHC molecules. This allows TCR therapy to target a broader range of cancer-associated proteins.