Radiolabelled VHH Fragments for Screening and Targeted Cancer Therapy
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Solution Overview
Problem
The heterogeneity of cancer in individuals poses a challenge for effective cancer treatment, necessitating methods to select subjects likely to respond to specific treatments.
Innovation Solution
Utilizing radiolabelled heavy chain variable domains (VHH) for both screening and therapeutic doses to identify and treat cancer cells, with imaging techniques to determine binding and administer isotopes like Iodine-131, Lutetium-177, Yttrium-90, Copper-67, Rhenium-186, or Rhenium-188 for targeted therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If different antibody fragments are used for screening and therapy, then treatment flexibility is improved, but treatment reliability deteriorates due to uncertainty in response prediction
Solution Approach 1:
The patent applies universality by using the same radiolabelled VHH fragment for both screening (diagnostic) and therapeutic functions. This multi-functionality ensures that the fragment tested during screening is identical to the one administered therapeutically, eliminating variability between different fragments and improving treatment response prediction reliability.
Solution Approach 2:
The patent implements preliminary action by performing screening with the radiolabelled VHH fragment before therapeutic administration. This preliminary binding confirmation ensures that only subjects whose tumors bind the fragment receive therapy, and since the same fragment is used for both purposes, it guarantees that the therapeutic agent will actually bind to the tumor, thereby improving reliability.
2Reliability
If screening is performed to identify suitable subjects, then treatment effectiveness is improved, but treatment time increases due to additional screening steps
Solution Approach 1:
The patent merges the screening (diagnostic) and therapeutic functions into a single radiolabelled VHH fragment. By combining these two previously separate steps into one agent, the screening process becomes integrated with the therapeutic process, reducing overall treatment time while maintaining effectiveness.
Solution Approach 2:
The radiolabelled VHH fragment serves dual purposes: it acts as both a diagnostic probe for screening and as the therapeutic agent. This multi-functionality eliminates the need for separate screening and treatment protocols, thereby reducing treatment time while ensuring effectiveness through binding confirmation.
3Reliability
If radioisotopes with both γ and β emission are used, then therapeutic effectiveness is improved, but radiation safety complexity increases
Solution Approach 1:
The patent uses radioisotopes that emit both γ and β radiation, allowing a single isotope to fulfill both diagnostic (γ imaging) and therapeutic (β radiation) functions. This multi-functionality improves therapeutic effectiveness by ensuring the same agent used for imaging is the one delivering therapy, while the radiation safety complexity, though increased, is managed through integrated protocols.
Data Source
AI summary
Provided herein are methods, kits, and compositions for stratifying and treating subjects, e.g., subjects having cancer. In some examples, the methods involve use of a radiolabelled heavy chain variable domain derived from a heavy chain antibody (VHH), or a functional fragment thereof, as both a screening agent and a treatment agent. In some examples, the VHH, or a functional fragment thereof, that is radiolabelled with a radioisotope that is both a γ-emitter and β-emitter.