SHANGHAI – Several weeks ago a 21-year-old man named Wei Zexi, diagnosed with terminal synovial sarcoma, a rare form of cancer of the soft tissue, died. In the weeks since his death, public debate and outrage have hit upon various elements of his story, illustrating a volatile mix of distrust in online transparency, lax oversight of regulations governing cell treatments and commonplace greed. It is also giving immunotherapy, a promising form of cancer treatment, a bad reputation in China.
Wei’s cancer was treated with DC-CIK immunotherapy at a military hospital in Beijing, a hospital he selected after it came up as a top result on the Chinese search engine, Baidu. The young man was reported to have paid ¥200,000 (US$36,000) for the treatment.
The first wave of recrimination has been hotly centered on Baidu, China’s premier online search engine. Before Wei died, he posted several touching videos sharing his plight. He also shared his dismay that the treatment he received had been ineffective and that Baidu’s top search result was in fact a paid advertisement for a private clinic. What has enraged the public is that Baidu’s search results are for sale, with the highest bidder getting top billing.
Wei sought treatment at the Second Hospital of Beijing Armed Police Corps, ostensibly a top-notch state hospital, but the hospital outsourced the key department to a for-profit group called the Biological Treatment Center. The owners of the center are said to hail from Putian, Fujian – local news reports stated 80 percent of China’s private hospitals are owned by people from Putian.
Baidu will be investigated for its sponsored search results by several government agencies, including China’s internet watchdog and the National Health and Family Planning Commission (NHFPC). The company has agreed to assist with the investigation.
But the controversy has taken its toll on Baidu’s Nasdaq-listed stock, dropping $20 from a high of $195 on April 15 to $175 as of May 6. Many in China are blaming part of the problem on lack of access to more independent search engines such as Google, which is blocked by the great firewall of China.
For-profits under military hospitals umbrella
The second wave of public concern has been targeting the practice of public and military hospitals outsourcing services to private clinics. In many cases, patients are unaware that the trusted state-backed hospital they are visiting is not managing their care.
The practice of outsourcing is banned for public hospitals and the NHFPC reiterated that in a recent notice. But the health ministry has no authority over the country’s network of military hospitals. Although that looks set to change, as the military has come under greater scrutiny as a part of President Xi Jinping’s anti-corruption campaign.
In March, China’s Central Military Commission issued a circular that plans were under way to terminate all commercial activities undertaken by the military. It is expected that the military hospital system – originally designed to care for military personnel – will no longer be able to treat civilians as a revenue-generating activity.
Dubious DC-CIK treatment
The latest focus of attention has been on the experimental cellular immunotherapy itself. Wei received dendritic cell cytokine-induced killer cells (DC-CIK).
DC-CIK is an untargeted treatment in which a low-dose T-cell cocktail is made from the patient’s extracted blood before being reinserted to boost the immune system to fight cancer. CIK cells are immune effector cells featuring mixed T- and natural killer cells. They are generated by incubating mononuclear cells with interferon-gamma, anti-CD3 antibody, recombinant human interleukin (IL-) 1 and recombinant human IL-2.
Dendritic cells act as messengers to deliver key information about invading pathogens and can help to activate killer cells. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system.
The DC-CIK is reported to have been developed by professors at Stanford University but fell out of favor in the U.S. to treat cancer when clinical trials failed to prove sufficient efficacy although the treatment is considered safe. That did not stop DC-CIK from becoming a cancer treatment in China, in violation of regulations that state it should not be used for clinical treatment and reserved for scientific research only.
There are currently 30 DC-CIK clinical trials listed on clinicaltrials.gov. Three trials list no location, while the remaining 27 studies originate in China.
Poor implementation of regulations
On May 6, China Daily, an English, state-run newspaper reported, “China’s top health authority reiterated on Thursday that the clinical use of immunotherapy for cancer treatment . . . (is) banned.” The article also was featured on the NHFPC English website. The English statement makes the mistake of conflating immunotherapy with cell treatments.
In fact, no cellular treatment has ever been approved as a mainstream clinical therapy in China. In 2009, cellular treatments were classified as third-class medical technologies, a category reserved for risky, experimental treatments permitted for research purposes if approved by a hospital ethics committee, treatment is provided free of charge and patients are fully informed of the study. Advertising of stem cell treatments is also barred, though a quick internet search shows that has not stopped.
In 2015, the ministry issued administrative measures on clinical research and applications that involve human stem cells, giving a role to the CFDA as well as NHFPC to oversee clinical trial development and further protect patients. (See BioWorld Today, Sept. 2, 2015.)
But as the Wei case illustrates, implementation of China’s rules remain a challenge.
China’s uncertain commercial path for cellular treatments, however, has not stopped Juno Therapeutics Inc. in creating a joint venture with Wuxi Apptec to bring the groundbreaking chimeric antigen receptor and T-cell receptor technologies here. And some experts are hopeful that the current controversy will pressure the government to formalize a new set of guidelines that will provide a regulatory path for commercial approval and the necessary expertise within the CFDA to do so. (See BioWorld Today, April 11, 2016.)