Humabody® Technology Applications

Humabody® Technology Applications

The Humabody platform is exceptionally versatile and has advantages in a broad range of both technology applications and disease areas. Crescendo is actively seeking to expand its partnerships in both of these areas.

MultiBody® Therapeutics

mAb Fusions

CAR-T

Humabody Drug Conjugates

Radionuclides

Oncolytic Viruses

Using its extensive in-house expertise, Crescendo is able to combine multiple Humabody VH into novel multi-specific formats that are expressed as a single construct. Crescendo can identify optimal configurations to access novel biology in ways that would be extremely challenging or impossible using whole antibodies. We have used this technology to generate our IO pipeline of T cell enhancing mulitspecifics.

  • Rapid assembly
  • Range of formatting options
  • Simple manufacture
  • Excellent biodistribution properties
  • Superior tissue penetration and accumulation compared to larger formats

Crescendo has shown that Humabodies can be quickly fused to any of the chains of an existing monoclonal antibody to generate novel multi-specific formats.

  • Rapid assembly
  • Adds functionality to existing therapeutic molecules
  • Simple manufacture

Typically, CAR-T therapies tend to use scFv as the targeting moiety; however, two-chain (VH/VL) formats can be prone to unfolding or misfolding, resulting in decreased activity or increased tonic signalling respectively.  Humabodies advantages compared to scFVs include:

  • Heavy chain only – single chain format avoids unfolding/misfolding of VH/VL
  • Small size – easily formatted into multispecifics, ideal for dual/multi targeting CARs
  • Preclinical data demonstrating that Humabody® VH domains can be used to generate highly effective CAR molecules, and that redirected Humabody CAR-T cells elicit potent killing activity in solid tumours have been published in the Journal for ImmunoTherapy of Cancer

Humabody VH are ideal for delivering potent, toxic payloads for treatment of solid tumours whilst maximising the therapeutic index. Crescendo has extensive in-house experience of optimally configuring Humabody molecules for delivery of toxic payloads. When compared to regular antibodies, formatted Humabodies at a drug antibody ratio (DAR) of just one (DAR=1) have shown:

  • Rapid, target-specific tumour penetration and accumulation
  • Rapid cellular internalisation
  • Improved tolerability

Humabody VH are ideal for delivering highly potent radionuclide payloads for the treatment of solid tumours whilst maximising the therapeutic index. Crescendo can optimally configure Humabody molecules which, when compared to regular antibodies formats, have shown:

  • Superior biodistribution
  • Rapid, target-specific tumour penetration and accumulation
  • Tuneable half-life minimising systemic exposure, limiting out-of-tumour toxicities

 

Humabody VH can be encoded as formatted ‘payloads’ within an oncolytic virus, delivering therapeutically active molecules directly into the tumour microenvironment.  Virus induced immunogenic cancer cell death combined with T cell engagement by Humabody VHs has the potential to unlock immune suppression in the tumour, turning immunologically ‘cold’ tumours ‘hot’.

  • Small size – ability to encode multiple single Humabodies, or multispecific Humabodies in viral vectors
  • Robust biophysical properties – can be stably produced and secreted from cancer cells at functionally relevant concentrations

To explore ways in which we could help you achieve your drug development goals, please contact us.