What HLA alleles can you generate pMHC antigens for?

We have experience with common Class I and Class II HLA alleles, and can have others custom-produced if needed. Our experts will guide you through the process to identify the most relevant allele based on your target population and peptide sequence.

How do you ensure the antibody is safe and doesn't recognize other peptides?

This is the core of our platform. We use a combination of in silico homology searches to identify potential off-targets and empirical screening against a panel of irrelevant or similar peptide-MHC complexes to prove specificity experimentally.

What if the natural affinity of the TCR for my target is very low?

This is a common challenge that our platform is designed to solve. Unlike natural TCRs, our antibody libraries contain 10^11 diverse paratopes, allowing us to isolate binders with affinities that are often 100- to 1,000-fold higher than the natural receptor, leading to superior potency.

TCR-Like Antibody Discovery Service by Premade Library

Screening Services Workflow Premade Libraries Cases Related Services Why Choose Us? Contact Us FAQ

Access the 90% of the human proteome invisible to traditional antibodies. We identify high-affinity, therapeutic-ready TCR-like antibodies that target intracellular antigens, opening a new era of drug discovery.

Target the Intracellular Proteome Look beyond the cell surface. Reach viral, mutated, or tissue-restricted proteins only displayed as peptide-MHC (pMHC) complexes, the language of health and disease spoken by every cell.	High-Affinity TCR Mimics Engineer antibodies that recognize pMHC targets with sub-nanomolar affinity, orders of magnitude tighter than natural TCRs for unparalleled therapeutic potency.
Unmatched pMHC Specificity Our platform is designed from the ground up to eliminate off-target recognition of related peptides or different HLA alleles, addressing the key safety challenge for this modality.	Human Formats Skip from discovery directly to development in fully human antibody fragments ready for conversion to CARs or other therapeutic formats.

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TCR-Like Antibody Discovery

Targeting the Untargetable. Illuminating the Intracellular.

The most compelling therapeutic targets (oncogenic drivers, viral proteins, autoimmunity mediators) lie deep within the cell, until now out of reach of antibody therapeutics. The cell's own antigen presentation system, however, offers a window into this world, displaying fragments of these proteins on its surface. At Creative Biolabs, we provide the key. Our service unlocks the inner world of the cell using massive antibody diversity and a proprietary screening platform that generates high-affinity biologics that can see what other antibodies cannot, expanding the realm of the possible.

Find Our Broader Epitope-Specific Discovery Capabilities

TCR-like antibody discovery is the pinnacle of epitope targeting. We apply similar principles of precision to other complex recognition challenges:

Fig.1 Premade Antibody Library based Anti-Idiotype Antibody Discovery. (Creative Biolabs Authorized)

Premade Antibody Library based Anti-Idiotype Antibody Discovery
Target the unique variable region of another antibody for critical PK/PD and immunogenicity assays.

Fig.2 Premade Antibody Library based Anti-PTM Antibody Discovery. (Creative Biolabs Authorized)

Premade Antibody Library based Anti-PTM Antibody Discovery
Isolate antibodies that recognize specific protein modifications, such as phosphorylation or glycosylation, to target unique functional states.

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Workflow

pMHC Target & Antigen Strategy

Peptide candidate selection; HLA allele choice; high-fidelity synthesis and biotinylation of stable pMHC monomers; design of null-peptide and irrelevant-peptide decoys.
Multi-Parameter Panning & Enrichment

Targeting pMHC monomer or tetramers; alternating panning between different pMHC batches; extensive depletion against peptide-free MHC and irrelevant pMHC complexes.
Clone Validation & Specificity Matrix

High-throughput screening of clones against a matrix of targets: the correct pMHC, irrelevant pMHCs, and empty MHC molecules. Confirmation by ELISA, BLI, or flow cytometry on peptide-pulsed cells. NGS analysis to identify diverse sequence families.
Antibody Production & QC

Conversion into scFv/Fab fragments or full IgG format for simplified downstream handling and characterization.
Affinity Maturation & Functional Validation

In vitro affinity maturation (if required) to achieve sub-nanomolar affinity.

Design Your Screening Strategy with Our Experts

Ready-to-Screen Antibody Libraries

The complexity of the pMHC surface demands a vast and diverse repertoire of paratopes to find the perfect molecular match. Our premier libraries are the source of the rare paratopes needed to recognize the complex pMHC interface.

Human Camel Llama Alpaca Humanized V_HH

Antibody Library ID	Display Technology	Library Format	Library Size
HuScL-6 ☆Highly Recommended	pIII-fusion, Phagemid Phage Display	Naïve scFv	2.1×10¹¹
HuScL-3S	pIII-fusion, Phagemid Phage Display	Semi-synthetic scFv	>1.0×10¹¹
HuFabL-4	pIII-fusion, Phagemid Phage Display	Naïve Fab	1.9×10¹⁰
HuFabssL-1	pIII-fusion, Phagemid Phage Display	Naïve & synthetic Fab	1.8×10¹⁰

Unsure which library is optimal for your pMHC target? Request a Quote

Case Study: High-Diversity Libraries, High-Impact Outcomes

TCR-Like Antibody Discovery (Peptide-HLA Complex)

Project Goal

To discover high-affinity antibodies that specifically recognize a tumor-associated peptide presented by the Target pHLA, while strictly avoiding binding to the same HLA allele presenting an irrelevant viral peptide (Control pHLA).

Project Challenge

This type of project is notoriously difficult due to the Framework Trap. The specific peptide surface area is minimal compared to the conserved HLA scaffold.

Initial Hurdle

We synthesized high-quality monomeric complexes and used them to screen our premade scFv library. An aggressive de-selection strategy using irrelevant peptide/HLA complexes was employed over five rounds of panning. In the first screening attempt (4 rounds), while enrichment was observed, the discrimination between the Target pHLA and Control pHLA was weak, indicating a high prevalence of non-specific HLA-framework binders.

Initial Output

From randomly picked clones, sequencing revealed 3 unique sequences. However, Soluble Phage ELISA confirmed that only 1 clone was specific, while 2 were cross-reactive (binding both Target and Control).

Fig.8 Graph illustrating the library screening outcomes. (Creative Biolabs Original)

Fig.9 Graph displaying the soluble ELISA validation results. (Creative Biolabs Original)

Our Solution

Recognizing the specificity challenge, our scientific team immediately optimized the panning strategy:

Enhanced Negative Selection: We significantly increased the ratio of the Control pHLA during the negative selection (depletion) phase to aggressively remove framework binders.
Stringency Modulation: We adjusted the washing stringency and input limits in the subsequent rounds to favor peptide-specific binding events.

Key Results & Data Visualization

Optimization Success	Following the strategy adjustment, Monoclonal Phage ELISA identified 3 new clones.
	Two clones exhibited robust, specific binding to the Target pHLA with no binding to the Control pHLA. One clone remained cross-reactive (serving as an internal control for the selection pressure).
	The specific clones were advanced to ELISA binding test and Surface Plasmon Resonance (SPR) analysis. SPR analysis confirmed robust, concentration-dependent binding using the steady-state model, validating the successful isolation of antibodies capable of distinguishing the peptide-MHC complex.

Ready to Build Your Success Story? Contact Us

Related Services

Find additional antibody discovery services tailored to your specific needs.

Fig.12 Functional human antibody discovery. (Creative Biolabs AI)

Functional Human Antibody Discovery

Fig.13 Anti-peptide/protein antibody discovery. (Creative Biolabs AI)

Anti-Peptide/Protein Antibody Discovery

Fig.14 Anti-Cell-based target antibody discovery. (Creative Biolabs AI)

Anti-Cell-based Target Antibody Discovery

Fig.15 Bi-functional antibody discovery. (Creative Biolabs AI)

Bi-functional Antibody Discovery

Fig.16 Cell-internalizing antibody discovery. (Creative Biolabs AI)

Cell-Internalizing Antibody Discovery

Fig.17 Anti-epitope antibody discovery. (Creative Biolabs AI)

Anti-Epitope Antibody Discovery

Fig.18 Antibody discovery for immunotherapy. (Creative Biolabs AI)

Antibody Discovery for Immunotherapy

Fig.19 Anti-disease-specific target antibody discovery. (Creative Biolabs AI)

Anti-Disease-Specific Target Antibody Discovery

Why Choose Us?

Pioneer the Intracellular Space

We provide a proven, industrialized platform to drug the pMHC target class, transforming targets previously considered undruggable into viable therapeutic programs.

Specificity by Design, Not by Chance

Our screening funnels are architected with specificity as the primary endpoint, employing rigorous counter-selection to mitigate the immense risk of off-target toxicity.

World-Class pMHC Antigen Production

We know pMHCs better than anyone and are experts in the most important and challenging step: the generation of stable, high-quality pMHCs to discover high-quality TCR-like antibodies.

Engineered for Therapeutic Translation

We are laser-focused on creating high-affinity, developable human sequences, ready for next-generation formats such as bispecifics, ADCs, and cell therapies.

Unmatched Speed to Validation

Our accelerated process provides functionally validated, high-affinity TCRm candidates in just a few months, allowing you to rapidly validate and prioritize hundreds of targets and speeding up your timelines significantly.

A Discovery Partner, Not Just a Platform

We offer not only a unique platform, but also unmatched expertise in immunology and antibody engineering, to support you in every step of this novel modality, from target selection to lead optimization.

Contact Us

Your most transformative targets are waiting. Partner with Creative Biolabs to develop the next generation of precision immunotherapies.

To provide you with a tailored proposal, please include the following:

Your target peptide sequence and its source protein
The desired HLA allele for presentation
The intended therapeutic application and mechanism of action
Any known challenges, such as peptide stability or homology
Your desired deliverables and project timeline

FAQ

What HLA alleles can you generate pMHC antigens for?
We have experience with common Class I and Class II HLA alleles, and can have others custom-produced if needed. Our experts will guide you through the process to identify the most relevant allele based on your target population and peptide sequence.
How do you ensure the antibody is safe and doesn't recognize other peptides?
This is the core of our platform. We use a combination of in silico homology searches to identify potential off-targets and empirical screening against a panel of irrelevant or similar peptide-MHC complexes to prove specificity experimentally.
What if the natural affinity of the TCR for my target is very low?
This is a common challenge that our platform is designed to solve. Unlike natural TCRs, our antibody libraries contain 10¹¹ diverse paratopes, allowing us to isolate binders with affinities that are often 100- to 1,000-fold higher than the natural receptor, leading to superior potency.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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