On April 20, Zhongshan Hengsai Biotechnology Co., Ltd. ("Hengsai Bio" for short) announced that it has completed the Pre-A round of financing of tens of millions of RMB. The funding is led by Fuho Capital, with the participation of Hengyue Investment, and MedBio Capital assuming the responsibility of the exclusive financial advisor.

Founded in 2018, Hengsai Bio is a high-tech enterprise focusing on tumor immunotherapy. It is mainly engaged in the R&D and industrialization of a new generation of individualized dendritic cell tumor treatment vaccine (DC vaccine).

What is the DC vaccine? What fields can it be applied to? Which stage of research progress does it hold currently? How huge the potential market is?

Dendritic cells (DC) are the most powerful antigen-presenting cells (APC) found at present. Their antigen-presenting function is much stronger than other antigen-presenting cells, such as macrophages and B cells. They have a sharp capacity to activate CD8+ and CD4+ T cells and can secrete a variety of cytokines to participate in immune regulation and response.

DCs were identified in 1973 by Professors Zanvil Cohn and Ralph Steinman. Professor Ralph Steinman treated himself with the DC vaccine for pancreatic cancer, which substantially extended his survival time. Hence, in 2011 Professor Ralph Steinman was awarded the Nobel Prize in Medicine for his pioneering work in identifying DCs. Substantial breakthrough in the DC vaccine has been obtained in the clinical research of tumor immunotherapy at home and abroad, and now, the DC vaccine has grown to be a fascinating research area in the field of tumor immunotherapy.

The theory of the DC vaccine preparation is very simple. DC precursor cells of patients are separated and cultured in vitro. Loading with tumor antigen, they are transferred to patients. Then, DCs stimulate specific anti-tumor T cells to make the anti-tumor effect come into play. Besides, DCs can establish a persistent anti-tumor-specific immune response, holding a critical position in anti-tumor immunity.

Since the anti-tumor properties of DCs remain consistent with the vaccine theory, DC therapy is mostly called DC vaccine clinically.

Research Progress of DC Vaccine

The first anti-cancer vaccine approved by FDA in 2010, Provenge (sipuleucel-T), was the DC vaccine. It is applied for the treatment of metastatic prostate cancer. Currently, various DC vaccines have been approved for marketing in the world, including CreaVaxRCC, Hybricell, DCVax-Brain, Provenge, and APCEDEN. The indications involve prostate cancer, malignant melanoma, renal cell carcinoma, non-Hodgkin's lymphoma, glioma, lung cancer, liver cancer, colorectal cancer, breast cancer, and nasopharyngeal carcinoma.

It deserves to be mentioned that Dendreo, which once developed Provenge, has a troubling sales condition in the later period on account of great production cost, complex operation, and marketing. In November 2014, the company declared bankruptcy because of heavy liabilities. Later, after rounds of twists and turns, SanPower Group, a private Chinese enterprise, finally acquired Provenge with US$ 819 million.

Till now, when the keyword "DC vaccine" is inputted in ClinincalTrials.gov for retrieval, a total of 256 trials on the DC vaccine can be reported. Both the ongoing clinical research and the marketing-approved DC vaccine have proved the possibility of it being innovative and effective immunotherapy for treating tumors.

Clinical Progress of DC Vaccine in Solid Tumors

Renal cell carcinoma

At the 2020 ASCO SITC Clinical Immuno-oncology Symposium, Immunicum released the latest data of Phase II clinical research MERECA of its DC vaccine, ilixadencel, on metastatic renal cell carcinoma (mRCC). The data showed that: as of December 2019, the survival rate of the ilixadencel treatment group was 54%, while that of the control group was 37%. The objective response rate (ORR) of the ilixadencel treatment group was 42% and that of the control group was 24%.

Glioblastoma

In April 2020, AIVITA analyzed the Phase II clinical trials (NCT03400917) of its candidate DC vaccine, AV-GBM-1, against glioblastoma (GBM). The results showed that: the overall survival rate of GBM patients (n=50) who received treatment with AV-GBM-1 was 76%, while that of the control group was 48%.

Small cell lung cancer

In March 2021, a randomized controlled Phase II trial of DC vaccine (Ad.p53-DC) for patients with recurrent small-cell lung cancer (SCLC) showed that the vaccine was safe, mainly with grade 1/2 toxicity and partial grade 3 toxicity. The positive immune response rates of different experimental groups ranged from 20% to 43.3%. Although the vaccine fails to enhance the objective response rates (ORRs) of patients under second-line chemotherapy, it still possesses the security and therapeutic immunity potential. As of the end of November 2021, there were 8 ongoing clinical trials of the DC vaccine for patients with lung cancer.

Prostate cancer

Another human Phase I/II trial of an adjuvant DC vaccine for high-risk prostate cancer patients after receiving radical prostatectomy presented results with great prospects. 5 of 12 patients with prostate cancer were relieved after 84 months, while the immune response of all patients was promoted. As of the end of November 2021, there were 5 ongoing clinical trials of the DC vaccine for patients with prostate cancer.

Currently, targeting solid tumors remain a critical challenge in tumor immunotherapy, and most innovative immune cell therapy technologies mainly focus on hematologic tumors. It is no doubt that the emergence of the DC vaccine shows a new direction for the immunotherapy of solid tumors.

DC Vaccine for the Treatment of COVID-19 Infection

Research has revealed that patients with coronavirus show moderate neutralizing antibody titer and T cell response falter, manifesting that it may be hard for conventional vaccine methods to produce long-term protection through a cellular immune response. As the most effective antigen-presenting cells in the human body, dendritic cells can present virus antigens to the immune system, to improve strong immune memory and offer years-lasting protection against the serious outcome of coronavirus infection.

Lineage Cell Therapeutics, a biotech enterprise that develops new cell therapies, has applied to the California Institute of Regenerative Medicine (CIRM) for funding in May 2020 to support the development of vaccines against SARS-CoV-2 with the company's allogeneic DC therapy platform, VAC.

Currently, the development of the COVID-19 vaccine at home and abroad grows vigorously. mRNA vaccines, DNA vaccines, inactivated viral vaccines, and recombinant adenovirus vaccines have been put on the market successively or are under clinical development. It is expected that the DC vaccine will become a member of the anti-pandemic arsenal as soon as possible.

Chinese DC Vaccine R&D Layout

NMPA has released such policies as Requirements for Registration Classification and Application Information of Biological Products (Trial), Guidelines for Acceptance and Examination of Registration of Therapeutic Biological Products (Trial), and Technical Guidelines for Research and Evaluation of Cell Therapy Products (Trial) to respond to the R&D trend of cell therapy including DC tumor vaccine, which indicates China's forward-looking requirements for encouraging and standardizing the overall cell therapy technology, including DC tumor vaccine.

With the implementation of policies, Chinese cancer vaccine projects have been followed up rapidly. Several enterprises have entered such a market. Among DC tumor vaccines based on tumor-associated antigens which are developed by enterprises led by HRYZ Bio Tech Co. and Shanghai Cell Therapy Group Co, Ltd., the first generation of DC vaccine takes Haixin Bio-tech as the fastest one, whose DC vaccines for colorectal cancer have entered clinical Phase III.

The second-generation DC tumor vaccine enterprises focusing on new antigens take Zskybio as a representative. Currently, Zskybio is advancing its clinical trials in China and the United States on a full scale, including the exploratory clinical research on new antigen DC vaccines for advanced malignant brain tumors, intestinal cancer, liver cancer, and pancreatic cancer. The company is expected to be the first new antigen DC tumor vaccine company in China to apply for IND.

The tumor vaccine is a hot research area in recent years, and its outstanding advantages provide new ideas for cancer treatment. Currently, most tumor vaccines are in the early clinical trial stage. Compared with other immunotherapy products, the prominent advantages of tumor vaccines are persistent anti-tumor immune response and high security, and there is no critical toxic reaction like cytokine release syndrome.

It is believed that with the R&D acceleration of the tumor vaccine and the advance in technical approaches, it is accessible to prevent and treat cancers with vaccination.

References:

1. Dendritic cell-based immunotherapy: a basic review and recent advances. Immunol Res, 2017.

2. https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0255-0.

3. Research progress on dendritic cell vaccines in cancer immunotherapy. Exp Hematol Oncol.2022; 11.

About  the Author:    

Yefenghong

Ye  Fenghong, a medical editor specializing in oncology at a healthcare internet  company, has conducted in-depth research on the pathogenesis and clinical  treatment of lung cancer and breast cancer. She has previously been involved  in the design and synthesis of anti-tumor drugs and has some experience in  computer-aided drug design. She is currently devoted to introducing  cutting-edge cancer treatment drugs to a wide range of readers, aiming to  help more people avoid cancer pain and embrace good health.