Minibody Generation Service

Creative Biolabs possesses unchallenged experience in diverse bispecific antibody (BsAb) generation, such as minibody. Our platforms cover fields from recombinant protein synthesis to epitope mapping, all of which are elaborately integrated for providing an expected minibody with desired specificity and affinity.

Genetic engineering is a widely used strategy to produce a variety of defined antibody fragments and novel proteins such as fusion proteins or immune-toxins. A useful strategy is to produce scFvs, which is composed of the variable regions of the immunoglobulin heavy and light chain, covalently fused by a peptide linker. These small proteins usually maintain specificity and affinity for antigen in a single polypeptide and enable to offer a convenient building block for larger, antigen-specific molecules. Nevertheless, on account of the small size of scFvs, they have limited applications as tumor-targeting agents in vivo, usually exhibiting very rapid clearance from the circulation in animal models. In order to get optimal tumor targeting, biodistribution, and clearance characteristics, antibody fragments of intermediate molecular weight are able to be developed to have the proper combinations of high tumor uptake and quick clearance from normal tissues.

Figure 1. Diagram of the structure of minibody and Tribi minibody.

Minibody

Minibody is composed of a pair of single-chain Fv fragments which are linked via CH3 domains, and Fvs with distinct specificity, which paired to the former part through heterodimerization process. To promote the heterodimerization efficiency, single-residue mutations can be introduced into each CH3 domains to achieve the “knobs and holes” approach. Far more than that, additional cysteine residues can also be introduced into CH3 domains to stabilize the bispecific minibody structure.

Tribi Minibody

As an enhanced version of minibody, Tribi minibody is an optimal tool in targeting tumor cells. One of its chains is designed to recognize tumor antigens via its two Fv fragments, while the other chain possessing a Fv fragment takes charge of recruiting effector cells, such as T cytotoxic cells or NK cells. With the addition of this extra binding domain, the avidity of Tribi minibody is significantly higher than that of the bispecific minibody. Thus, even at a lower concentration, Tribi minibody is still able to perform a stronger cytotoxicity than the corresponding bispecific minibody.

With our well-established minibody generation platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique minibody products. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Hu, S. Z.; et al. Minibody: a novel engineered anti-carcinoembryonic antigen antibody fragment (single-chain Fv-CH3) which exhibits rapid, high-level targeting of xenografts. Cancer research. 1996, 56(13): 3055-3061.
2. Pandit-Taskar, N.; et al. First-in-Human Imaging with 89Zr-Df-IAB2M Anti-PSMA Minibody in Patients with Metastatic Prostate Cancer: Pharmacokinetics, Biodistribution, Dosimetry, and Lesion Uptake. Journal of Nuclear Medicine. 2016, 57(12): 1858-1864.