Analyzing structure and interactions
JASCO Circular Dichroism (CD) spectroscopy, can play a crucial role in understanding and optimizing CAR-T cell therapy by analyzing the structure and interactions of key components.
Specifically, CD spectroscopy can be used to characterize the protein structure of the CAR, the hinge region, and even exosomes involved in the process, which can help in designing more effective CAR-T therapies. Here's four areas of interest:
1. Understanding CAR Structure and Function:
CARs (Chimeric Antigen Receptors):
CD spectroscopy can help analyze the structural conformation of the CAR protein, particularly the single-chain variable fragment (scFv) and intracellular signaling domains, which are crucial for target recognition and T-cell activation.
Hinge Region:
The hinge region connects the scFv to the transmembrane domain and its flexibility impacts CAR function. CD can be used to study the structure and conformational dynamics of the hinge region.
Exosomes:
Exosomes, released by both cancer cells and CAR-T cells, can be analyzed using CD to understand their role in cell-to-cell communication and their potential as biomarkers or delivery vehicles in CAR-T therapy.
2. Optimizing CAR Design:
Improved Binding:
By analyzing the structure of the scFv using CD, researchers can potentially improve its binding affinity to cancer cell targets, leading to more efficient tumor targeting.
Enhanced Signaling:
Understanding the structure of the signaling domains can help optimize their activation pathways, leading to more potent T-cell activation and tumor cell killing.
Stability and Folding:
CD can be used to assess the stability and folding of CAR proteins, ensuring they remain functional under different conditions.
3. Monitoring and Quality Control:
Protein Folding:
CD can be used to assess the proper folding of CAR proteins during manufacturing, ensuring the quality and efficacy of the final product.
Stability and Degradation:
CD can be used to monitor the stability of CAR proteins over time and under various storage conditions.
4. Potential Applications in Solid Tumors:
Exosome Profiling:
CD can be used to profile exosomes derived from solid tumors, potentially identifying specific mutations and biomarkers that can be targeted by CAR-T cells.
Microenvironment Studies:
CD can be used to study the structural changes in proteins and other biomolecules within the tumor microenvironment, which can help researchers understand how to overcome the immunosuppressive effects and improve CAR-T cell efficacy in solid tumors.
In summary, CD spectroscopy is a valuable tool for understanding the structural details of key components involved in CAR-T cell research, such as the CAR protein, the hinge region, and exosomes. This knowledge can then be used to design more effective and targeted CAR-T therapies, especially for solid tumors, and to improve the manufacturing and quality control of the therapeutic product.
JASCO Therapeutic Antibodies - Application eBook
The market for therapeutic antibodies has been dramatically expanding over the past decades. Antibody drugs exhibit therapeutic effects, such as inhibiting the growth of malignant tumor cells and the activity of immune cells by binding antigens expressed in target cells with high affinity and specificity. Such antibody drugs are expected to be effective therapeutic agents for unmet medical needs.
The higher order structures (HOS) formed by therapeutic antibodies determines their efficacy. Because antibodies are unstable macromolecules, their HOS can be affected by various stimuli during the manufacturing process, resulting in reduced drug efficacy and impurities derived from the target substance. Therefore, HOS is considered to be a Critical Quality Attribute (CQA) and is subject to similarity studies, stability studies, and forced degradation studies in the R&D process from target assessment to lead optimization. In addition, it is monitored during the post-launch manufacturing process.
Antibody structures are hierarchically formed as primary, secondary, tertiary, and quaternary structures, and it is important to comprehensively evaluate each structure in the characterization of antibodies. This application eBook presents examples of evaluations using various analytical instruments, including Circular Dichrosim (CD) spectrometers, Fourier-transform infrared (FTIR) spectrometers, Raman imaging microscopes and High Performance Liquid Chromatography (HPLC).
JASCO Circular Dichroism
Download related Application Notes, Article & Poster
JASCO Circular Dichroism
Watch JASCO Webinars
Basics of Protein Secondary Structure Analysis using FTIR and Circular Dichroism Spectroscopy
Orthogonal Similarity Assessment of Monoclonal Antibodies Using Circular Dichroism, FTIR and Raman
CD for Experimental Investigation & Verification of Protein Structure in the AlphaFold Era
Circular Dichroism - A Webinar on Sample Considerations and Parameter Optimization
JASCO opens the door to the future of Circular Dichroism
JASCO has produced the highest quality circular dichroism instrumentation for over 50 years. The J-1000 series is the result of many advances in technology combined with a great deal of customer input. These three new models are adaptable to meet any requirements and can be expanded as applications or budgets evolve.
The innovative optical system of the J-1700 allows the measurement of a CD spectrum in the near-IR region up to 2,500 nm using an unique Triple Detection system. JASCO J-1700 is ideal for structural analysis of metal complexes and colored proteins, magnetic CD spectra measurements of transition metals and CD measurements of the first and second overtones of vibrational transitions
JASCO J-1500 allows the measurement of a CD spectrum in the vacuum UV region down to 163 nm. The vacuum UV region below 200 nm, is of critical importance for biomolecules, particularly in protein secondary structure estimation.
High sensitivity combined with a maximum of 10,000 nm per minute scan speed allows the J-1700/J-1500 to measure samples quickly increasing productivity in your lab. An additional benefit is the minimal time exposure of biological samples to the high-energy UV light minimizing the risk of sample degradation.
Stray light will result in distortion of the CD spectrum, particularly in the Far-UV region where the sample absorbance is high. The dual polarizing prism optical design equipped in the J-1000 Series results in stray light lower than 0.0003% enabling them to obtain high quality CD data even under conditions with high absorbance.
The latest Quad Lock-in Amplifier allows the simultaneous acquisition of up to four data channels including CD, Absorbance, Linear Dichroism (LD), Fluorescence, Fluorescence detected CD (FDCD), Fluorescence detected LD (FDLD), Fluorescence Anisotropy and Optional Rotatory Dispersion (ORD).
Designed as a “Chiroptical Spectroscopy Workbench” the J-1500 offers a wide range of accessories to allow it to be adapted to any application requirements. Temperature ramping, protein folding, enzyme kinetics, DNA/RNA interactions, natural organic chemistry, biochemistry, macromolecules and rapid scanning experiments are all possible.
The J-1100 offers the basic cell holders for general CD/LD/Abs and Temperature control measurements.
Chiroptical spectroscopy has become one of the most important techniques for the characterization of biomolecules, determination of absolute configuration and stereochemical analysis. Since launching our first spectropolarimeter in 1961, JASCO has designed and built the finest in chiroptical instrumentation.
To learn more about how JASCO technology
could assist in your research please contact us on
freephone 0800 773 274 or email: info@specsci.nz