T-cell receptor (TCR-T) therapy, which involves the utilization of TCRs that bind to human leukocyte antigens (HLA) and whose target range can be greatly expanded to include cytoplasmic and nuclear proteins, is a promising option for the treatment of pancreatic cancer. Alfa Cytology aims to utilize decades of experience and deep expertise in TCR biology to expand the potential of cellular therapies.
Overview of TCR-T Cell Therapy for Pancreatic Cancer
TCR-T therapies use heterodimers composed of α and β peptide chains to recognize peptide fragment molecules presented by MHC. Unlike chimeric antigen receptor (CAR) T-cell therapies that target surface antigens, TCR-T cells recognize intracellular antigens processed and presented by MHC molecules. This expands the range of antigens that can be targeted and allows for the targeting of cancer-specific mutations or neoantigens. Recently, researchers found that using a single infusion of genetically modified autologous T cells could target the mutated KRAS G12D HLA-C binding epitope and treated a patient with progressive metastatic PDAC.
Fig. 1 TCR-recognized tumor antigens. (Shafer P, et al, 2022)
In addition, several preclinical studies have explored the efficacy of TCR-T cell therapy in pancreatic cancer. Notable advances include:
- Targeting Mutant KRAS: TCR-T cells designed to target the KRAS G12D and G12V mutations have been observed to enhance tumor regression in mouse models.
- MUC1 as a Target Antigen: MUC1-specific TCR-T cells were able to recognize and kill pancreatic tumor cells, thereby prolonging survival in animal models.
Our Services
Alfa Cytology's one-stop TCR-T cell therapy development service provides a comprehensive, integrated approach to preclinical research. Our research focuses on the discovery, development and manufacture of highly specific and potent next-generation TCR-Ts to target pancreatic cancer-specific proteins.
Antigen Identification and Characterization Service
Target Discovery
Identify tumor-specific antigens associated with pancreatic cancer, including neoantigens and shared tumor antigens.
Comprehensive Profiling
Detailed molecular and immunological characterization of identified antigens is provided to assess their applicability as targets for TCR-T cell therapy.
TCR Discovery Services
TCR Screening and Isolation
We use a high-throughput screening platform to isolate TCRs with high affinity and specificity for pancreatic cancer-related antigens.
TCR Sequencing and Cloning
State-of-the-art technologies are used to accurately sequence, clone and functionally analyze identified TCRs.
Comprehensive TCR Characterization
Evaluation of binding affinity, specificity and cross-reactivity of identified TCRs.
TCR Engineering Services
Genetic Engineering
We offer cutting-edge genetic modification services to engineer TCRs into patient T cells, including the use of viral vectors, CRISPR/Cas9, and other gene-editing technologies.
Affinity Optimization
Rational design and directed evolution techniques are used to optimize TCR affinity, enhancing the therapeutic efficacy while minimizing the risk of off-target effects.
Customized TCR Constructs
We develop and optimize customized TCR constructs tailored to specific antigens and patient profiles, including the generation of bispecific TCRs for multi-targeted approaches.
Preclinical Efficacy Study Services
- In Vitro Functional Assays: Comprehensive in vitro assays, including cytotoxicity, cytokine release and proliferation assays, are performed to assess the functional efficacy of engineered TCR-T cells against pancreatic cancer cells.
- In Vivo Efficacy Testing: Our preclinical models, including patient-derived xenografts and syngeneic tumor models, provide robust platforms for assessing the antitumor activity, safety, and biodistribution of TCR-T cells.
- Safety and Toxicology Assessments: Evaluate the safety of TCR-T cells, including potential off-target effects and immunogenicity, to ensure a smooth transition to clinical development.
By utilizing advanced technologies and a comprehensive development process, Alfa Cytology aims to deliver highly specific and effective TCR-T cell therapies. Our comprehensive development services ensure that our clients receive the highest quality R&D support, paving the way for future therapeutic success. Contact us today to learn more about the services offered.
Reference
- Shafer P, et al. Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects. Front Immunol. 2022, 13:835762.
