PtLnX™: Pt-based Conjugation

Antibody-drug conjugates (ADCs) are complex bio-macromolecules combining the accurate targeting capability of a monoclonal antibody with the extremely high cytotoxicity of a payload drug via a molecular linker. As a potent new candidate for next generation cancer immunotherapy, ADCs have been demonstrated both by concept and in practice to accurately deliver the payload drugs only to the antigen bearing cells, minimizing the collateral damage to normal tissues and reducing the side-effects of otherwise highly toxic agents.

Bridging an antibody and a payload drug, the molecular linker is a key ingredient in the formation of an ADC. A good linker should bear a simple structure and be chemically compatible with both the antibody and the payload drug. It not only contributes to the stability and solubility of the ADC, but also dictates the release mechanism of the payload drug inside the cell. Up to this date, various linkers with high chemical complexities have been exploited but they all exert certain drawbacks that prevent their wide application in ADC developments.

Set out to the search for a chemically simple yet versatile linker, we encountered a unique coordination compound: bis(ethylenediamine) platinum chloride [Pt(en)Cl2] a few years back. Now, after extensive exploration and experimentation, Creative Biolabs has established a platform centered with Pt(en)Cl2 and we are proud to announce our innovated PtLnX™ conjugation platform for ADC developments!

What is PtLnX?

PtLnX is a technical platform developed by Creative Biolabs and one of our collaberators that uses bis(ethylenediamine) platinum chloride [Pt(en)Cl2] as a linker core for ADC development.

How does it work?

Pt(en)Cl2 is a coordination compound that forms stable linkages with nitrogen-containing organic alkaline (N-Alk) such as N-heteroaromatic and N-aliphatic amine, including Histidine residues on an antibody. Under suitable conditions, we can easily conjugate an antibody with a payload drug containing N-Alk modules by just using Pt(en)Cl2.

 Working scheme of PtLnX linker. PtLnX linker is usually conjugated with payloads to form PtLnX-payload complexes, which are subsequently conjugated to antibodies to form PtLnX ADCs. Working scheme of PtLnX linker. PtLnX linker is usually conjugated with payloads to form PtLnX-payload complexes, which are subsequently conjugated to antibodies to form PtLnX ADCs.

Why PtLnX?

PtLnX linker, Pt(en)Cl2, is a short, non-cleavable linker with a Pt metal core. Previously, it has been applied in protein conjugation for the preparation of kinase inhibitor-albumin and kinase inhibitor-lysozyme conjugates for hepatic and renal targeting. Comparing to many currently available linkers, PtLnX linker is highly advantageous:

  • Metal salt-like core structure endues PtLnX linker with excellent solubility, enabling conjugation reactions to take place in aqueous solutions and prevent ADC aggregations.
  • Conjugation reactions occur rapidly under neutral or slightly basic pH environment (7.0~8.5), preserving antibody activity. Pt(en)Cl2 is also compatible with most of the common buffer systems (phosphate buffer, HEPEs…).
  • PtLnX linker is compatible with various payload drugs that contain N-Alk modules, such as auristatin F, tubulysin, maytansinoid…
  • PtLnX linker mediated conjugation occurs on antibody Fc-region His residues, resulting in ADCs with narrow drug to antibody ratio (DAR) distributions.
  • Being small in size and non-cleavable, PtLnX linker has excellent serum stability.
  • PtLnX linker conjugated ADCs have shown similar antigen binding affinity as the unconjugated monoclonal antibodies.
  • PtLnX ADCs have shown enhanced in vivo efficacy and expanded therapeutic window comparing to other ADCs with same payloads.

What we offer?

Creative Biolabs offers full ADC development and licensing services using PtLnX platform. Our services include but not limited to:

1. Basic PtLnX conjugation chemistry—test the feasibility of conjugation, chemical QC (purity, pI, serum stability) of the conjugated ADC, and assay for target affinity (SPR, Lindmo) and FcRn affinity (SPR).
2. In vitro evaluation of PtLnX ADC—analysis for target cell internalization, efficacy, and off-target toxicity.
3. In vivo evaluation of PtLnX ADC—assay for efficacy in tumor bearing mice and evaluate for bio-distribution and maximum tolerated dose.
4. Licensing the PtLnX ADC for new drug development.

Highly advantageous, PtLnX could be a key for the development of next-generation ADCs and eventually, help the course for fighting cancer and numerous other diseases. Creative Biolabs is dedicated to promote PtLnX to a wider audience so please contact us for more specifications and collaboration!

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