Frontiers and Opportunities: Highlights of the 2nd Annual Conference of the Chinese Antibody Society

Abstract

The Chinese Antibody Society (CAS) convened the second annual conference in Cambridge, MA, USA on 29 April 2018. More than 600 members from around the world attended the meeting. Invited speakers discussed the latest advancements in therapeutic antibodies with an emphasis on the progress made in China. The meeting covered a vast variety of topics including the current status of therapeutic antibodies, the progress of immuno-oncology, and biosimilars in China. The conference presentations also included the development of several novel antibodies such as antibodies related to weight loss, T-cell receptor-mimicking antibodies that target intracellular antigens, and tumor-targeting antibodies that utilize both innate and adaptive immune pathways. At the meeting, the CAS announced the launch of its official journal—Antibody Therapeutics—in collaboration with Oxford University Press. The conference was concluded by a panel discussion on how to bring a therapeutic drug developed in China to the USA for clinical trials. Statement of SignificanceThe CAS convened the second annual conference in Cambridge, MA, USA on 29 April 2018. The meeting covered a variety of topics, including therapeutic antibodies being tested in clinical trials, new antibodies (e.g., programmed cell death protein 1/programmed death-ligand 1 inhibitors) being developed in China, and T-cell receptor-mimicking antibodies that target intracellular antigens.

Development of bispecific antibodies in China: overview and prospects

“…HX009 consists of human IgG4-Fc of anti-PD-1 mAb and ECD of SIRPα, and can achieve the anti-tumor synergistic effects by simultaneously activating innate and adaptive immune responses and also by suppressing tumor immune escape by inhibiting the immune checkpoint [ 97 ]. The other candidate bispecific therapeutic, IBI322, was showed that its binding affinity to PD-L1 was stronger than that to CD47, implying a potential therapy to PD-L1-positive cancers [ 129 ].…”

Antibodies to watch in 2019

“…Chinese companies are engaging with FDA, and developing their product candidates according to the standards of the FDA and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (www.ich.org). 49 In particular, Chinese companies have progressed multiple antibodies targeting PD-1 into late-stage studies and regulatory review in China, including tislelizumab, sintilimab and camrelizumab.…”

The approval of sintilimab for classical Hodgkin's lymphoma: views and perspectives of anti-PD-1/PD-L1 antibodies in China

“…Sintilimab achieved 77.6% of progression-free survival at 6 months for patients with cHL [ 1 ], and the efficacy appears to be comparable to that of nivolumab (77%) and pembrolizumab (69%) [ 2 , 3 ]. Dr. Michael Yu, the chairman, CEO and president of Innovent Biologics, commented that sintilimab, a novel full human IgG4 antibody targeting PD-1 generated by yeast display method, has 10–50 folds higher binding affinity to PD-1 than nivolumab and pembrolizumab [ 4 ] and pharmacodynamics analysis in cHL patients showed greater than 95% PD-1 receptor occupancy [ 1 ]. Based on the data of crystal structure of sintilimab/PD-1 complex [ 4 ], sintilimab appears to bind to PD-1 in a unique conformational epitope with highly complementary, hydrophobic surfaces formed by antibody complementarity-determining regions (CDRs), distinct from nivolumab and pembrolizumab.…”

“…Dr. Michael Yu, the chairman, CEO and president of Innovent Biologics, commented that sintilimab, a novel full human IgG4 antibody targeting PD-1 generated by yeast display method, has 10–50 folds higher binding affinity to PD-1 than nivolumab and pembrolizumab [ 4 ] and pharmacodynamics analysis in cHL patients showed greater than 95% PD-1 receptor occupancy [ 1 ]. Based on the data of crystal structure of sintilimab/PD-1 complex [ 4 ], sintilimab appears to bind to PD-1 in a unique conformational epitope with highly complementary, hydrophobic surfaces formed by antibody complementarity-determining regions (CDRs), distinct from nivolumab and pembrolizumab. The area of the interactive hydrophobic surfaces on sintilimab is almost double those on nivolumab or pembrolizumab, with seven cluster-distributed alkyl–π interactions identified when bound to PD-1.…”

“…These characteristics confer a significantly slower off-rate to sintilimab compared to nivolumab or pembrolizumab. Moreover, high rates of CD8 + T cells vs. T reg cells and CD8 + T vs. CD4 + T cells were observed in both preclinical mouse model [ 5 ] and human subjects and improved the ratio of effector T cell populations that may contribute to the mechanism of action of sintilimab.…”