Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. HLX10, a fully humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro, and anti-tumor activity in several tumor models. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. To elucidate HLX10’s mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. Notably, HLX10’s epitope was closer to Pembrolizumab’s epitope than Nivolumab’s epitope. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo, providing a rationale for clinical evaluation in cancer immunotherapy.

Using a dynamic version of the present value model and a range of developed and Asian emerging markets, this article considers estimates of stock market prices given expectations on dividends and earnings and compares these fundamental stock prices with actual stock prices. The reported empirical results suggest that a dynamic present value model combined with differing definitions of cash flows can explain actual stock price movements for many of the sample markets. For markets where price deviations from fundamental value are statistically significant, the revealed deviations are investigated by considering types of investor behaviour which might drive such departures.

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The standard theory of asset pricing, in which a long-run relationship should exist between stock prices and dividends if there are no deterministic explosive bubbles, assumes the constancy of expected returns. However, the investor'se x p e c t e dr e t u r n sa r e more likely to be time varying, which have led to the modification for the tests of rational bubble. One modification is that the tests should be applied to the log levels of stock price and dividend for allowing the detection of the stochastic explosive root bubble, which incorporates the possibility of time-varying expected returns. Accordingly, we test the existence or otherwise of both types of rational bubbles in the Asian stock markets by applying the unit root tests and the cointegration analyses. The empirical results suggest that the rational bubbles exist in the stock markets of Japan, Singapore, Korea, Taiwan, Thailand, Malaysia, Indonesia and Philippine, whereas Hong Kong is found to have no rational bubbles.