World famous immunologist Chen Lieping, a professor at Yale University, was invited to the Institute of Biophysics of the China Academy of Sciences (CAS) to give a lecture on Jan 16, 2017.
Before the lecture, CAS academician Rao Zihe presented him with the top award of the Biophysical Society of China (BSC) – the Shitsan Pai Award -- in recognition of his pioneering contributions to cancer immunotherapy.
Rao Zihe presents the Shitsan Pai Award to Chen Lieping (L) at the Institute of Biophysics, CAS, Beijing, on Jan 16. [Photo/bsc.org.cn]
In his lecture, Future Cancer Immunotherapy: Enhancement or Normalization of Immunity, Chen focused on the basic principle of immune response to tumors, explaining the progress in tumor immunity treatment with his own research and clinical experience of more than 20 years. Chen analyzed two different perspectives for tumor immunity treatment, namely, immune response enhancement and immune response normalization, and predicted potential research trends for the future.
Chen gives a lecture. [Photo/bsc.org.cn]
Most current tumor immunotherapy uses immunity enhancement to control tumors through amplifying the immune response. The common methods used to enhance tumor immunity include cytokines such as IL-2 and interferons (IFNs), cancer vaccines such as Provenge. antibodies like anti-CTLA-4 and anti-4-1BB, and adoptive cell therapies such as CAR-T and TCR-T, according to Chen.
However, the approach of enhancing immunity is generally of limited effectiveness. Provenge for example, can only prolong the life span of a prostate cancer patient by 3-4 months. In addition, the immune response enhancement is quite similar to that of chemotherapy -- both may cause severe side effects and have a negative impact on the body. With the former approach the patient may not be able to experience immune response enhancement while the latter may require an increase in dosage to the maximum that the patient could bear, Chen added.
The audience in the packed lecture hall [Photo/bsc.org.cn]
More than 20 years ago, Chen observed that tumors of most patients kept growing after the patients receive the tumor vaccine, and their immune response and iymphocytes still increased.
He speculated that this phenomenon may be caused by the immunodeficiency of the tumor microenvironment, so he started to look for the molecular cause of the immunodeficiency.
In 1999, Chen and his team found and cloned B7-H1 (later referred to as PD-L1). B7-H1 (PD-L1) has structures similar to the immunoglobulin protein on the surface of tumor cells. In 2000, B7-H1 (PD-L1) was combined with the programmed death receptor PD-1.
In 2002, Chen was the first to discover that overexpression of B7-H1 can cause lessening of tumor immunity and tested the therapeutic effects of anti-PD-L1 monoclonal antibodies. In 2006, he initiated anti-PD (anti-PD-1/PD-L1) antibody therapy, which led to the first antibody drug for clinical treatment of tumors being approved by the FDA in 2014.
In honor of these pioneering discoveries Chen Lieping was given the William B. Coley Award (2014), the top international tumor immunology award, and an American Association of Immunologists Stanley Manchester Award (AAI-Steinman Award) (2016).
The anti-PD antibody treatment developed by Chen is different from other cancer immunotherapies: it targets the tumor microenvironment and repairs the immune deficiency induced by tumors so as to normalize the immune response. The anti-PD antibody treatment has ideal therapeutic effect for almost all terminal solid tumors and some liquid tumors (invalid on the part of leukemia); it can make the tumor shrink and disappear and has a lasting effect with low toxicity (only 5 percent of patients suffer side effects). The only drawback is that the treatment is not effective for some conditions, such as lung cancer. The anti-PD only takes effect in 30 percent of patients. Chen is dedicated to finding the reasons behind this treatment resistance and has made progress in that regard.