Cell Therapy Proteins

Mammalian-Expressed Catalog & Custom Peptide-MHC Complexes

Class I and Class II Alleles

Product Features

Choice of Allele

Biotinylation & Fluorescent Labels

Verified Bioactivity

Shop by Allele

Class I Alleles – Human

Class I Alleles – Mouse

Class II Alleles or Other Alleles

For other class I alleles, non-classical alleles, or class II alleles click here

Shop by Peptide Sequence

Custom Peptide

For MHCs with custom peptide sequences,click here.

Alternatively, try a Peptide-Ready MHC to load your peptide in-house onto an MHC tetramer or monomer.

Product Validation Data

Human NY-ESO-1 (HLA-A*02:01) Tetramer

Anti-NY-ESO-1 (HLA-A*02:01) Antibody, hFc Tag captured on CM5 Chip via Protein A can bind Human NY-ESO-1 (HLA-A*02:01) Tetramer, His Tag with an affinity constant of 0.09 nM as determined in SPR assay (Biacore T200).

Human KRAS G12V (HLA-A*03:01)

Human KRAS G12V (HLA-A*03:01) , His Tag captured on CM5 Chip via anti-his antibody can bind Anti-KRAS G12V (HLA-A*03:01) Antibody with an affinity constant of 0.11 μM as determined in SPR assay (Biacore T200).

Biotinylated Human P53 R175H (HLA-A*02:01)

Immobilized Anti-P53 R175H (HLA-A*02:01) Antibody, hFc Tag at 5μg/mL (100μL/well) on the plate. Dose response curve for Biotinylated Human P53 R175H (HLA-A*02:01) , His Tag with the EC50 of 1.6μg/mL determined by ELISA.

Human NY-ESO-1 (HLA-A*02:01) Tetramer

As verified by ELISA, the activity of NY-ESO-1 (HLA-A*02:01) tetramer expressed in mammalian cells and E. coli is comparable, providing you with more choices for research.

Peptide-Ready MHC: Load your own peptide

Load your own MHC monomer or tetramer in-house with our peptide-free MHCs.

→ Quick & simple peptide loading procedure

→ Monomer / Tetramer

→ Fluorescent Labeling

→ Class I and Class II Alleles

→ Biotinylation

MHC Product Types

Monomers

Our MHC peptide monomers are mammalian-expressed to ensure the natural configuration and have a His-Avi tag at the C-terminus. The Avi tag is a 15-amino acid sequence, which has a high affinity for biotin and can be specifically biotinylated by BirA.

Tetramers

MHC tetramers are complexes of four peptide-MHC biotinylated monomers bound to streptavidin molecules. The enhanced avidity of MHC tetramers and TCR interactions can have a significant impact for detecting antigen-specific T cells. They allow for direct detection, phenotyping, and enumeration of antigen-specific T cells within a polyclonal T cell population. KACTUS offers class I and class II tetramers.

Fluorescent Tetramer

Fluorescent MHC tetramers can be used to identify T cells that recognize a particular peptide-MHC complex. By labeling T cells with MHC tetramers, the frequency and distribution of antigen-specific T cells can be determined and sorted by FACS in a cell population. MHC tetramers can also be used to monitor immune responses to vaccines, infections and diseases by measuring the frequency of antigen-specific T cells over time to track the efficacy of a treatment.

MHC-I Virus-Like Particles

In combination with our Virus-Like Particles (VLP) technology platform, we have introduced multivalent fluorescent MHC I. These MHC I-VLP complexes are about 750 Å in diameter, compared to the MHC I monomer size of 70 Å. Each VLP contains approximately 250 copies of MHC I, resulting in boosted fluorescence quantum yield for enhanced detection of TCR binding. We currently offer FITC- and APC-equivalent options for MHC I-VLP fluorescence labeling.

Peptide-Ready MHC

Neoantigens offer a distinct advantage in their unique tumor-specific and normal tissue-absent feature, presenting ideal targets for effective and personalized tumor-specific immunotherapy. We have developed Peptide-Ready MHCs (prMHC), which are composed only of the α heavy chain and β2-microglobulin (β2m) light chain for loading your own neoantigen.

Chimeric MHC

Chimeric MHCs have the human α3 immunoglobulin-like domain replaced with the mouse α3 domain. This modification enhances antigen specificity for antibody discovery. These mammalian-expressed Chimeric MHCs retain their normal conformation to increase the likelihood of generating peptide-specific antibodies while decreasing the frequency of non-specific antibodies and making screening less labor-intensive.

Custom MHC Complexes

Choice of mammalian or E. coli expression systems

Monomers, Tetramers, Biotinylation, Fluorescent Labels

Multi-faceted biological activity verification (ELISA, SPR, FACS, etc.)

Choice of Class I or Class II Alleles

Choice of PE, APC, or other fluorescent label

Various species: Human, mouse, monkey, etc.

Soluble TCR Expression & SPR Analysis

→ Production of various formats of soluble TCRs, including scFv-TCR, TCR-His, etc.

→ TCR engineering to optimize soluble TCR expression based on TCR modeling

→ SPR analysis of soluble TCR & Peptide-Ready MHC/Peptide-MHC interactions

HLA-G and LILRs

→ HLA-G Monomers and Tetramers

→ LILRAs and LILRBs

→ APOE Proteins

→ Custom HLA-G & LILR Proteins

Major Histocompatibility Complex

The MHC (Major Histocompatibility Complex) is a major histocompatibility complex, which is a highly polymorphic family of cell surface proteins, also known as HLA in humans. MHC can bind to peptide fragments of intracellular antigens to form MHC-peptide complexes, which are then transported to the cell surface and recognized by the corresponding T cell receptor (TCR) to initiate an immune response.

In humans, the main types of MHC involved in antigen presentation are MHC I and MHC II. MHC I, after binding antigen peptides, is recognized by CD8+ T cells, while MHC II, after binding peptides, is recognized by CD4+ T cells. MHC-peptide complexes represent a category of intracellular antigen targets. Their unique binding pattern with TCR plays a crucial role not only in adaptive immune processes but also holds significance for TCR-related therapies such as TCR-T development.

Mechanism of MHC involvement in antigen presentation (Anthony W. Purcell, et al., 2019)

MHC Class I (MHC-I)

MHC-I molecules play a crucial role in the immune system by presenting peptide antigens to cytotoxic T cells. These heterotrimers consist of a transmembrane MHC heavy chain, a light chain known as β2-microglobulin (β2m), and an 8-10 peptide antigen. The heavy chain contains two peptide binding domains (α1 and α2), an immunoglobulin-like domain (α3), and a transmembrane region. The folding of the α1 and α2 domains forms a groove where peptide antigens bind to the MHC-I molecule. β2m stabilizes the peptide binding groove and MHC I presentation.

A single nucleated cell expresses 5×10⁵ copies of each MHC I molecule, presenting a variety of peptides simultaneously on the cell surface to CTLs. Accumulating genomic mutations in cancers result in the production of tumor-specific antigens or neoantigens, which can be presented by MHC I molecules of tumor cells to CTLs.

MHC Class 1 complex (MHC-I) containing an α-chain spanning the cell membrane and an extracellular β2m (β2-microglobulin) connected to this chain.

References

1. Kurosawa et al., Development of a T‐cell receptor mimic antibody targeting a novel Wilms tumor 1‐derived peptide and analysis of its specificity. Cancer Sci. 2020 Oct; 111(10): 3516–3526.

2. Doubrovina et al., Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope-specific HLA-restricted T cells with cytotoxic activity against WT-1(+) leukemias. Blood. 2012 Aug 23;120(8):1633-46

What are prMHCs?

KACTUS peptide-ready MHCs (prMHC) are MHC monomers and tetramers absent of antigenic peptides. The prMHCs are stabilized and ready for loading the neoantigen peptide of your choosing. They are ideal for generating custom MHC peptide tetramers and high throughput peptide screening. The prMHCs are expressed from HEK293 cells and have >95% purity.

Do you offer a peptide-loading protocol?

KACTUS offers a quick and simple protocol for loading peptides in-house. Contact us to receive the protocol.

Class I Peptide-Ready MHC (prMHC).

What can I do with a prMHC?

Shop Alleles

Browse available alleles in our stabilized peptide-free form.

Performance Validation of prMHCs

Figure 1. Demonstrated via ELISA assay, biotinylated Human Peptide Ready HLA-A*11:01&B2M Monomer loaded peptide (VVVGADGVGK) has a high affinity with HLA-A*11:01&B2M&KRAS G12D TCR. The EC50 is 110 ng/mL.

Figure 2. Demonstrated via SPR assay, biotinylated Human Peptide Ready HLA-A*11:01&B2M Monomer loaded with peptide (VVVGADGVGK) has a high affinity with HLA-A*11:01&B2M&KRAS G12D TCR. The affinity constant is 8.5 nM.

Figure 3. Demonstrated via SPR assay, Human Peptide Ready HLA-A*02:01&B2M& Monomer loaded with peptide (FMNKFIYEI) has a good affinity with HLA-A*02:01&B2M&AFP TCR. The affinity constant is 0.32 µM.

Figure 4. Demonstrated via FACS assay, fluorescent-labeled Human Peptide-Ready HLA-A*02:01&B2M Tetramer loaded with peptide (SLLMWITQC) can bind with HLA-A*02:01&B2M&NY-ESO-1 TCR cells.

Stability Testing of KACTUS prMHCs

Freeze Thaw Stability

KRAS G12D peptide was added to biotinylated human HLA-A*11:01 and freeze thawed up to five times. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2μg/mL (100μL/well). Results are a dose response curve for Biotinylated
Human KRASG12D (HLA-A*11:01), His Tag with EC50s of 0.22/0.16/0.18/0.15/0.15/19 μg/mL.

Biotinylated human HLA-A*11:01 was freeze-thawed up to five times after which KRAS G12D peptide was added. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2μg/mL (100μL/well). Results are a dose response curve for Biotinylated Human KRASG12D (HLA-A*11:01), His Tag with EC50s of 0.21/0.13/0.18/0.16/0.16 μg/mL.

Stability Testing at 4C

KRAS G12D peptide was added to biotinylated human HLA-A*11:01 and incubated at 4℃ for 0, 7, 14, and 21 days. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2µg/mL (100µL/well). Results show a dose-response curve for Biotinylated Human HLA-A*11:01&B2M&KRAS G12D (VVVGADGVGK) monomer, His Tag with EC50s of 0.19/0.11/0.13/0.14/0.16 µg/mL.

Biotinylated human HLA-A*11:01 was incubated at 4°C for 0, 7, 14, and 21 days, after which KRAS G12D peptide was added. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2µg/mL (100µL/well) on the plate. Results show a dose-response curve for Biotinylated Human HLA-A*11:01&B2M&KRAS G12D (VVVGADGVGK) monomer, His tag with EC50s of 0.16/0.11/0.26/0.32/0.36 µg/mL.

Stability Testing at 37C

KRAS G12D peptide was added to biotinylated human HLA-A*11:01 and incubated at 37℃ for 0, 1, 3, and 5 days. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2µg/mL (100µL/well). Results show a dose response curve for biotinylated human KRAS G12D (HLA-A*11:01), His tag with EC50s of 0.19/0.22/0.16/0.22/0.29/10.56 µg/mL.

Biotinylated human HLA-A*11:01 was incubated at 37℃ for 0, 1, 3, and 5 days, after which KRAS G12D peptide was added. Activity was analyzed via ELISA. Immobilized TCR was added to the plate at 2µg/mL (100µL/well). Results show a dose-response curve for Biotinylated Human KRAS G12D (HLA-A*11:01), His tag with EC50s of 0.19/0.22/0.52/0.46/0.43 µg/mL.

Neoantigen Peptides and Their Role in MHC/TCR Interactions

Neoantigens are highly specific targets and ideal targets for immunotherapy. Degraded neoantigen peptides can bind with major histocompatibility complex (MHC) molecules, forming complexes that are subsequently transported to the cell surface. These complexes are recognized by T-cell receptor (TCR), triggering an immune response. MHC polypeptide complexes constitute a category of neoantigen targets, and their distinctive interaction with TCR holds immense importance in the advancement of neoantigen-based immunotherapies, including TCR-T cell therapy, antibody drugs, and tumor vaccines.

Identification of the affinity of peptide loaded MHC with TCR [1].

prMHC FAQs

Our Products

About Peptide-Ready MHCs

Expression of prMHCs

Fluorescent Labeling

Protocols & Applications

References

Novel Combination of Targets in Immune Response and Drug Discovery

Figure 1. LILRB binding ligands.

HLA-G

MHC-I proteins present antigenic peptides and are recognized by associated receptors. This enables the immune system to detect self-antigens and eliminate targets lacking self-antigens or expressing foreign antigens. Human leukocyte antigen G (HLA-G) is a non-classical human MHC class Ib molecule. It is an important immune tolerance molecule in the body, contributing to immune escape or immune cell anergy. In recent years, it has been regarded as a new type of immune checkpoint.

HLA-G, like other immune checkpoints, mediates its function by binding to receptors on immune cells. The known receptors of HLA-G are leukocyte Ig-like receptor subfamily B member 1 (LILRB1) and member 2 (LILRB2) which belong to the Leukocyte Ig-like receptor (LILR) family. LILRs are one kind of these receptors that either activates (LILRA members) or suppresses (LILRB members) immune cell functions. When HLA-G binds to LILRBs, tumor cells can escape the surveillance of the immune system. As LILRBs have a similar immunoreceptor tyrosine-based inhibitory motif (ITIM) like immune checkpoint proteins such as CTLA4 and PD-1, they’ve become hot targets for drug development, especially for discovery of first-in-class drugs.

Multiple clinical/preclinical studies show the potential broad anti-tumor effects of LILR family proteins, such as BND-22 (Biond), IO-202 (Immune Onc), JTX-8064 (Jounce Therapeutics) and NC410 (NextCure). In addition, since the expression profile of HLA-G is significantly different from that of PD-L1, HLA-G antibodies might be able to enhance tumor sensitivity to anti-PD-L1 therapy. This would be a novel breakthrough for patients with tumors that do not respond to anti-PD-L1 therapy.

Performance Validation

Figure 2. Human LILRB2, hFc Tag captured on CM5 Chip via Protein A can bind Human HLA-G&B2M&Peptide (RIIPRHLQL) Tetramer with an affinity constant of 4.62 nM as determined in SPR assay (Biacore T200).

Figure 3. Rhesus macaque LILRB1, hFc Tag captured on CM5 Chip via Protein A can bind Rhesus macaque HLA-G&B2M&Peptide (RIIPRHLQL) Tetramer, His Tag with an affinity constant of 1.74 nM as determined in SPR assay (Biacore T200).

Figure 4. Cynomolgus LILRB2, His Tag immobilized on CM5 Chip can bind Cynomolgus HLA-G Complex Tetramer, His Tag with an affinity constant of 852 nM as determined in SPR assay (Biacore T200).

Figure 5. Serial dilutions of Anti-LILRB2 Antibody were added into Human LILRB2, His Tag : Biotinylated HLA-G Complex Tetramer, His Tag binding reactioins. The half maximal inhibitiory concentration (IC50) is 75.3ng/ml.

Product Lists

HLA-G Products

KACTUS has developed a full portfolio of mammalian-expressed HLA-G monomers and tetramers including biotinylated versions. Our HLA-G monomers and tetramers are mammalian-expressed from HEK293 cells and have >95% purity with low endotoxin (<1EU/ug). HLA-G monomers and tetramers can be used for antibody discovery, TCR binding, and flow cytometry. We also offer custom HLA-G tetramers. Contact us today to learn more.

LILRA, LILRB, and APOE Products

Using our SAMS protein engineering platform, we have developed a large portfolio of LILRA and LILRB catalog products. These products are expressed from HEK293 cells and are available in multiple species, including human, mouse, cynomolgus, and rhesus macaque as well as biotinylated versions. Contact us today to request a custom LILR.

Research-Grade & Preclinical-Grade Laminin 521

Matrix protein for maintenance of pluripotent stem cells.

KACTUS has successfully developed a high-quality Laminin 521 product that can be applied to scientific research (research-grade) and preclinical development (preclinical-grade). It can effectively support the normal growth and passage of PSCs, maintain good stemness, and ensure the homogeneous growth of cells with genetic stability. Laminin 521 can be applied to the cultivation of stem cells and other primary cells and the development of related stem cell products.

Available Products

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KACTUS Laminin 521 Features

Use on Various Cell Types

Applicable to a wide range of cells: iPSCs, hMSCs & most anchorage-dependent progenitor cell types

Expect Quality

> 95% Purity

Low Internal Toxicity (<10EU/mg)

Transition to Feeder-Free Culture

Compatible with a variety of feeder-free stem cell culture media

Maintain Growth

Maintain homogeneous growth and karyotype stability of stem cells

Recombinant Laminin for Stem Cell Culture

Due to their unique ability for self-renewal and directional differentiation, stem cells can be applied in many fields such as embryonic development research, drug screening modeling, and cell therapy. At the same time, stem cell culture methods continue to be optimized. Laminin 521 is an important matrix adhesion protein, which can recreate a suitable growth environment for primary cells such as stem cells, and is currently one of the most commonly used trophoblast-free culture substrates.

Figure 1. The main components of globular basement membrane (GBM) [2].

Laminin 521 can maintain the pluripotency of stem cells, promote cell proliferation, support the clonal expansion of pluripotent human stem cells and the growth of skin keratinocytes. It is also involved in the regulation of important physiological processes such as cell adhesion, migration, differentiation, phenotype maintenance, and matrix-mediated signal transduction [3]. Compared with Laminin 511, Laminin 521 can support the monolayer maintenance and expansion of stem cells in the absence of apoptosis inhibitors (such as ROCK inhibitors). It can be an excellent alternative to Laminin 511 and to some extent, is more suitable for human pluripotency stem cell culture than Laminin 511.

What are the applications of Laminin 521?

Stem Cell Expansion Culture

Laminin 521 can support the low-density growth and self-renewal of stem cells in a chemically defined, animal-free environment. It is suitable for the culture of hSC, iSC and cloned stem cells, such as hPSC [4], MSC, hematopoietic stem cells, etc.

Directed Differentiation of Stem Cells

Laminin 521 promotes the differentiation of hPSCs into different cell types such as hepatocytes, cardiomyocytes, retinal pigment epithelial (RPE) cells [5] and endothelial cells [6]. hESCs grown on Laminin 521 can exhibit molecular phenotypic characteristics of hepatocytes and undergo cell self-organization [7].

Organoid Culture

Indeterminate media replacing Matrigel is a major target for organoid culture, and full-length laminin (rather than laminin-derived peptides) has been shown to be a key component for the correct formation of organoids in gel models. Lucendo-Villarin and collaborators developed an economical automated platform for the generation of human hepatic spheroids from pluripotent stem cell-derived hepatic progenitors, endothelial cells, and hepatic stellate cells with the help of laminin 521, which can be used in disease modeling and drug screening research [8].

Growth Maintenance of Differentiated Primary Cells

Laminin 521 can support the growth and proliferation of differentiated primary cells, such as cardiomyocytes, retinal pigment epithelial (RPE) cells, nerve cells, endothelial cells, islet cells, etc. For example, the basement membrane damage of the isolated islets will cause islet function decline and cell death, but when cultured on a matrix containing Laminin 521, it can significantly promote the survival and function maintenance of islet cells [9], and has now been successfully applied in the original Generation islet cell culture system. Likewise, cardiac progenitor cells differentiated in vitro can proliferate on Laminin 521-containing matrices and transform into mature cardiomyocytes.

Drug Research

Laminin 521 is a new anti-GBM disease pulmonary hemorrhage autoantibody target. Studies have shown that in anti-glomerular basement membrane disease, circulating antibodies can recognize Laminin 521 in addition to type IV collagen, indicating that Laminin 521 is Another major autoantigen against GBM [10], autoantibodies against Laminin 521 may promote lung injury and lead to pulmonary hemorrhage by increasing the total amount of IgG bound to the alveolar basement membrane, which provides theoretical clues for the development of related drugs.

Maintain Expression of Stem Cell Markers & iPSC Growth In Vitro

KACTUS Laminin 521 was pre-coated with 0.5µg/cm² in a 6-well dish, seeding the thawed iPSC cells at a concentration of 1×10⁴/cm². After 5 days of culture, stem cell markers were detected via flow cytometry.

Figure 2. Normal expression of stem cell markers OCT3/4, SOX2, SSEA4, TRA-1-60, etc.:

Figure 3. Laminin 521 can effectively maintain the growth of human iPSCs.

What is Laminin 521?

Laminin 521 (LN521, LAMB2, LN-11) is a heterotrimeric glycoprotein composed of α5, β2 and γ1 chains, expressed in stem cells and most basement membranes (especially in the nerve sheath, muscle nerve junction and glomerular basement membrane GBM). It is a key matrix protein that supports the growth of stem cells and maintains the stability and performance of the basement membrane.

Laminin 521 can form a huge net-like material environment together with nestin, collagen, fibronectin, glycosaminoglycan, and other extracellular matrix components. It is a key supportor of various tissues such as muscle fiber, epithelium, nerve, capillaries, fat, etc. In addition, the LG1-5 region of Laminin 521 can bind to cell membrane surface integrin α6β1 or α3β1, etc., start the downstream PI3K-Akt signaling pathway, and promote cell proliferation.

Figure 4. Laminin 521 structure [1].

How do I use Laminin 521?

General recommended procedure:

1. Coat the cell culture flask/dish with Laminin 521 (a typical dosage is 0.5 μg/cm² but this can vary depending on the experiment).

2. Wash the cells and incubate with digestive enzymes or EDTA.

3. Separate into a single cell suspension, centrifuge, and resuspend in appropriate fresh medium.

4. Seed cells on culture flask/dish coated with Laminin 521.

References

About CAR-T Therapy

Chimeric antigen receptor-modified T-cell (CAR-T) therapy is a novel immunotherapy approach that has achieved remarkable success in the treatment of a variety of hematological malignancies. The basis of CAR-T therapy is to make the immune system attack cancer cells. Briefly, patient T cells are isolated and genetically engineered to express a chimeric antigen receptor (CAR) that recognizes specific tumor-associated antigens (TAAs) such as CD19, a cell surface protein that is uniformly and strongly expressed on malignant B cells. Two new FDA-approved CD19-specific drugs, KymriahTM and YescartaTM, demonstrate the importance of TAAs in CAR-T cell therapy research.

Utilizing our SAMSTM platform, KACTUS has developed a series of recombinant proteins covering multiple CAR-T cell therapeutic targets, including difficult-to-express proteins such as CD19 and BCMA. We offer various types of highly active CAR-T target antigen proteins, including site-directed labeled proteins, fluorescent labeled proteins, biotin-labeled proteins, etc., which can flexibly meet different research and development needs such as CAR-T positive rate detection.

Performance Validation

Human FITC Compatible CD19

Figure 1. Use Human CD19-FITC Compatible protein to detect the expression rate of Anti-CD19-CAR positive cells. Non-transfected 293T cells and FITC-labeled protein control were used as negative control.

PE-Labeled Human EGFR VIII

Figure 2. 293T-CAR Cells were incubated with PE-Labeled Human EGFR VIII, His Tag and PE-labeled protein control. Non-transfected 293T cells and PE-labeled protein control were used as negative control.

Biotinylated Human MSLN

Figure 3. Anti-MSLN CAR-293T cells were incubated with Biotinylated human MSLN-hFc-Avi Tag. Non-transfected 293T cells and Fc-labeled protein control were used as negative control. SA-FITC was used to evaluate the binding activity of Biotinylated Human MSLN.

Service Features

Production of various formats of soluble TCRs, including scFv-TCR, TCR-His, etc.

TCR engineering to optimize soluble TCR expression based on TCR modeling

SPR analysis of soluble TCR & Peptide-Ready MHC/Peptide-MHC interactions

SPR Characterization Services to Combat TCRs with Low Binding Affinity

TCRs often have low binding affinity to Peptide-MHCs (pMHC) which makes characterization via ELISA difficult. Alternatively, SPR is well suited for characterizing TCRS with low binding affinity. In addition to soluble TCR expression, we also offer SPR analysis services for characterizing the binding between TCRs and Peptide-MHCs or Peptide-Ready MHCs.

TCR Binding with Peptide-Ready MHC & Peptide-MHC

(A)

(B)

(C)

Figure 1. HLA-A*02:01 neoantigen loading efficiency in Peptide-Ready MHC loaded with FMNKFIYEI peptide (A), Peptide-MHC with FMNKFIYEI peptide (B), and MHC with no peptide (C).

Peptide-MHCs, Peptide-Ready MHCs, & Soluble TCR Expression

Get full support for your TCR therapy drug development endeavors with our comprehensive customized TCR and Peptide-MHC complex expression services.

Expression Validation: gp100 TCR & Anti-CD3 Bispecific Fusion Protein

Figure 2. We have successfully expressed Tebentafusp, which not only binds to the GP100 (HLA-A*02:01) complex but also simultaneously binds to CD3 heterodimers, demonstrating excellent bidirectional binding activity. In ELISA (left) and SPR (right) analyses, Tebentafusp can bind to both monomers and tetramers of Human GP100 (HLA-A*02:01) complex, with an EC50 and affinity constant of 11.8 ng/mL and 0.196 nM, respectively.

About TCR Therapy

What is TCR Therapy?

TCR therapy is a novel immunotherapy developed based on the recognition pattern between the body’s TCR and antigens. It includes two forms: T cell transfer therapy (TCR-T) and TCR protein drugs (TCR-scfv, TCR mimic antibodies, etc.). Among them, the principle of TCR-T involves first screening and validating TCR sequences that can recognize antigens. Through genetic engineering, these sequences are integrated into the patient’s T cells, equipping them with the ability to selectively bind to and eliminate tumor cells expressing the target antigens. In this context, “antigen” refers to complexes formed by MHC (or HLA) with intracellular antigen peptides. Through this unique recognition mechanism, TCR-T can target a wider range of intracellular antigens, leading to more pronounced effects in solid tumors.

Figure 3. TCR Recognition of MHC-Peptide Complex [2]

Figure 4. TCR-T Treatment Process [3]

Advantages of TCR Therapy

High specificity and sensitivity are prominent features of TCR-T therapy, especially in generating robust T cell responses against low-density antigen populations. Additionally, it exhibits a lower probability of cytokine release syndrome. Furthermore, compared to CAR, TCRs often possess lower affinity and faster dissociation, enabling continuous triggering of recognition responses and facilitating the amplification of immune signals.

CR-scfv & TCR Mimic Antibodies

TCR-scfv (single chain variable fragment) and TCR mimic antibodies represent a novel class of protein engineering techniques, focusing directly on the development of protein drugs using TCR or TCR-like structures. This approach eliminates the need for genetic engineering and T cell transfer, resulting in a simpler manufacturing process and providing a more streamlined treatment option for clinical use. A representative drug in this category is Tebentafusp, currently the only approved TCR therapy on the market. It can simultaneously recognize the GP100 peptide-(HLA*02:01) complex and CD3.

Figure 5. TCR-T Treatment Process [3]

References

[1] http://www.scgcell.com/

[2] Natarajan K, Jiang J, May NA, Mage MG, Boyd LF, McShan AC, Sgourakis NG, Bax A, Margulies DH. The Role of Molecular Flexibility in Antigen Presentation and T Cell Receptor-Mediated Signaling. Front Immunol. 2018 Jul 17;9:1657.

[3] Tsimberidou AM, Van Morris K, Vo HH, Eck S, Lin YF, Rivas JM, Andersson BS. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors. J Hematol Oncol. 2021 Jun 30;14(1):102.

[4] Chandran SS, Klebanoff CA. T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance. Immunol Rev. 2019 Jul;290(1):127-147.