P106 The Efficacy and Safety of Bevacizumab Combined with Chemotherapy in the Treatment of Drug-Resistant SCLC

Abstract

different receptors, multi-specific antibodies with the capacity to blockade of multiple targets or binding sites are showing improved therapeutic efficacy against cancer. Although "knobs-into-holes" technique is an efficient way to generate bispecific antibody with whole IgG-architecture, the efficacy of different heavy chain hetero-generation and the thermostability remain questionable. How to efficiently generate tetra-specific antibodies with more efficiency and stability is critical for the development of novel antibodies against cancer. Method: By using the structure-based computational design and longtime molecule dynamic simulation (5 ms), we have successfully developed a more efficient technique "Lock-and-key" to produce bispecific antibodies with more efficiency. Based on the parent EGFR antibody cetuximab, PD-L1 antibody atezolizumab, VEGF antibody bevacizumaband CTLA-4 antibody ipilimumab, EGFR tetra-specific antibody with whole IgG structure was designed. Results: With the benefits of multispecific antibody and whole IgG architecture, the EGFR tetra-specific antibody could specifically target EGFR, PD-L1, VEGF and CTLA-4, exhibiting potent anti-tumor efficacy than the combination of Cetuximab, Atezolizumab, Bevacizumab and Ipilimumab against NSCLC. Conclusion: "Lock-and-Key" technique could be a more promising method to produce the multi-specific antibody. More importantly, multi-specific antibody with whole intact IgG structure shows the advantages in cancer treatment. Antagonism of EGFR, PD-L1, VEGF and CTLA-4 through multi-specific antibody could be a promising anti-tumor strategy against NSCLC. Keyword: Multi-specific antibody, nonsmall cell lung cancer, tumor microenvironment