Bispecific Antibody Application in Radioimmunotherapy

Creative Biolabs has substantial work experience in the design and manufacture of payload-delivered bispecific antibody (BsAb) products with empirically proven high affinity. We are confident in offering best-in-class BsAbs to fulfill your immunoradiotherapy program development needs thanks to the efforts of Creative Biolabs' experienced professionals.

Introduction to Radioimmunotherapy

Radioimmunotherapy is a type of targeted cancer therapy in which radiolabeled antibodies are utilized to deliver deadly radiation to tumor cells. A basic targeting approach involves delivering radioactivity to tumor cells by antibodies that target antigens expressed by tumor cells. Pretargeting approaches separate the administration of the antibody from the subsequent delivery of the radionuclide, reducing the radionuclide's residence time in the blood, which is the primary source of dose-limiting hematologic toxicity. In animal model systems, including solid and hematologic cancers, pretargeting methods exhibit decreased hematologic toxicity and greater efficacy.

Applications of BsAbs in Radioimmunotherapy

Research started with the development of a BsAb made from two Fab fragments, one against TAA and one against DTPA loaded with indium, which was later shown to be effective in pretargeting xenograft tumor models by increasing the radiation dose absorbed by the tumor. An anti-CD20-bispecific fusion protein constructed by an anti-CD20 antibody and an anti-chelated radiometal trap for a radiolabeled ligand (yttrium [Y]-DOTA) captured by a very high-affinity anti-Y-DOTA scFv antibody. The CD20 BsAb showed efficacy in the treatment of subjects with Ramos or Granta subcutaneous lymphoma, with a significant reduction in myelosuppression. In animal models, all animals that received optimal doses of the CD20 BsAb were cured after 150 days, whereas tumor growth in control animals progressed rapidly and became a complete disease after 25 days. Among the reported BsAbs used for radioimmunotherapy, commonly used TAA targets include CEA, CD38, GD2, HER2, PSMA, mesothelin, hK2, etc., and hapten-peptides including HSG, DFO, etc. In addition, a variety of antibody formats have been developed, including IgG, Fab-Fab, Tri-Fab, scFv-scFv, etc.

Advantages

Using a BsAb as the primary targeting agent is a promising pretargeting strategy that has substantially improved the therapeutic efficacy and reduced the toxicities of radioimmunotherapy. BsAbs employ a novel radiolabeled hapten-peptide system that may be tailored to bind a wide range of therapeutic and imaging radionuclides. Furthermore, fully humanized BsAbs can be created, which are significantly less immunogenic than an antibody conjugate or recombinant protein including streptavidin or avidin. Another potential advantage of the BsAb technique is that it does not require an additional step to remove or block the primary targeting antibody prior to the addition of the radiolabeled peptide.

Our Services

As a global company, Creative Biolabs is delighted to display our advanced integrated engineering platform, which ensures cost-effective and time-saving BsAb services for all clients. Our experienced and well-trained experts are here to assist you in your research.