Current Landscape of Cancer Immunotherapy

  • Posted on: Mon, 01/02/2017 - 22:42
  • By: admin

“Current landscape of cancer Immunotherapy” consists of a series of reports synthesized and written by the Life Science Division. We selected 34 companies that have a major focus on cancer immunotherapy. By examining their pipeline, science, and performance, we report on the recent advancements in five categories of cancer immunotherapy: checkpoint inhibitors, cell therapy, therapeutic antibodies, cancer vaccines, and immune cell modulators.

Project Team Composition


Linda Zhao (project leader) , Feng Wang, Xi Chen, Liu Zhang

Project Status


Completed

Delivered Report

We composed a series of reports, each highlighting one category of cancer immunotherapy: immune checkpoint modulators, immune cell therapy, therapeutic antibodies, cancer treatment vaccine, and immune system modulators. Please contact us admin@ochis.org if you are interested in accessing these reports.

Cancer Immunotherapy

Modern healthcare improves the average lifespan of humans. However, as people live longer, new problems arise. People are more likely to suffer from cancer with aging. This takes years or even decades to develop, as normal cells gradually accumulate the necessary tumorigenesis driver mutations. Before 19th century, there were other diseases like cholera and plague, which took lives of millions of people around the world. But now, cancer has become one of the biggest killers, which ranks second to cardiovascular disease [1]. According to the statistics from WHO, there were approximately 14 million new cases and 8.2 million cancer related deaths worldwide in 2012, and moreover, the number of new cases is expected to rise by about 70% over the next two decades [2]. Cost-wise, the total economic burden of premature death and disability due to cancer worldwide was about $0.9 trillion in 2008, which represents 1.5% of the global GDP. The economic toll from cancer is almost 20% more than that of cardiovascular disease [3]. The huge mortality and economic burden associated with cancer, has brought it into prominence for policy makers, pharmaceutical companies, and researchers.

However, big data doesn’t have to be terabytes volume level but rather be a comprehensive data sets containing all possibly collectible data, which may or may not be directly related to the research topic. One advantage of this could be the repeatable use of same data for different studies. Comparing with conventional sample study, the cost of conducting a big data study may be higher, but accuracy and precision of conclusion would be significantly improved. On the other hand, big data focuses more on correlation among the data rather than causality, which may help scientists discover unexpected mechanism of diseases.

Most human cancers are treated by conventional treatments such as surgical resection, chemotherapy, and radiation. Surgery was applied to ∼45% of all patients with cancer, whereas chemotherapy and radiation therapy together account for 5%. Surgery is usually more effective in preventing cancer recurrence in digestive organ cancer. However, it cannot be applied to certain cancers, such as leukemia [4]. In addition, it is also very hard to use surgery to treat metastatic cancers. Chemotherapy and radiation, especially the former one, can damage surrounding cellular tissue, as they lack the ability to differentiate between healthy and cancerous tissue. Nowadays, the tremendous advances achieved in the understanding of intricate molecular mechanisms underlying malignant progression of human cancer have delivered unprecedented progress in novel therapeutics development. The characterization of proteins associated with tumours presents opportunities for targeted therapeutic interventions, and this approach is called “targeted therapy” [5]. However, the heterogeneity of tumours limits the clinical success of targeted therapy. Thus, improved “targeted therapy”, as well as other new treatments are being developed. In cancer biology, the well-known hallmarks of cancer comprise of ten biological capabilities. One of the most recently identified is ability to “avoid immune destruction”. Additionally, research in immunology has shown that monoclonal antibodies can recognize targets with great specificity and affinity. Thus re-activating and employing immune system or antibodies are considered as one potential method for treating cancer.

Immunotherapy is harnessing the immune system to treat cancer. The first indications that the immune system might respond to cancerous tissue were reported in 1890 [6]. After that, the feasibility of cancer immunotherapy was not clear for a long time. It now appears that overwhelming evidence is available to support the view that both the innate and adaptive immune responses can recognize and eliminate tumours. In the past few years, the fast-growing field of cancer immunology has generated new ways of curing cancer. Many research institutes and pharmaceutical companies were involved in these investigations. These methods can be grouped into five classes listed below [7], and the current status and key players of which will be analyzed in a series of reports.

Immune Checkpoint Modulators

Certain proteins, called immune checkpoint proteins, are able to limit the strength and duration of immune responses. Therefore, blockade of immune checkpoint proteins can activate the immune system to destroy cancer cells. By now, the Food and Drug Administration (FDA) has approved four checkpoint inhibitors, including the CTLA-4 inhibitor ipilimumab (advanced melanoma), the PD-1 inhibitors nivolumab and pembrolizumab (advanced melanoma), and the PD-L1 inhibitor atezolizumab (bladder cancer).

Immune Cell Therapy

Adoptive cell transfer (ACT) is another immunotherapy that has been tested in clinical trials. Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapy are two strategies in this category. Tumor-infiltrating lymphocytes are collected from tumor samples, and then amplified in the laboratory. The cells are subsequently activated by treatment with cytokines and then infused into patient’s bloodstream. CAR T-cell approach is to collect patients’ T cells, which are then genetically modified to express a protein known as a chimeric antigen receptor, or CAR. A large number of modified cells are infused into the patient to attack cancer cells.

Therapeutic Antibodies

Therapeutic antibodies are antibodies are designed to bind certain targets to kill cancer cells. Compared with other small molecule drugs, antibodies are more specific. Furthermore, the therapeutic antibodies can be combined with other radioactive compounds, which are called antibody–drug conjugates (ADCs), and it has been shown that ADCs are particularly effective. The FDA has approved several ADCs for the treatment of patients with cancer. Other therapies combine non-antibody immune system molecules and cancer-killing agents.

Cancer Treatment Vaccine

Cancer treatment (or therapeutic) vaccines belong to the third class of immunotherapy. These vaccines are usually made from a patient’s own tumor cells or from substances produced by tumor cells. They are designed to strengthen the body’s natural defense to fight against cancers that have already developed.

Immune System Modulators

The last class is the so called “Immune System Modulators”, which uses proteins that normally help regulate, or modulate, immune system activity to enhance the body’s immune response against cancer. These proteins include cytokines and certain growth factors. Two types of cytokines are used to treat patients with cancer: interleukins and interferons.

References

[1] http://www.who.int/mediacentre/factsheets/fs310/en/index2.html

[2] Global cancer statistics, 2012. (2015) Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. CA Cancer J Clin. 65(2):87-108.

[3] The Global Economic Burden of Non-communicable Diseases. WHO report.

[4] Nanotechnology applications in surgical oncology. (2010) Singhal S, Nie S, and Wang MD. Annu Rev Med. 61: 359–373.

[5] Novel delivery approaches for cancer therapeutics. (2015) Ashim K. Mitra, Vibhuti Agrahari, Abhirup Mandal, Kishore Cholkar, Chandramouli Natarajan, Sujay Shah, Mary Joseph, Hoang My Trinh, Ravi Vaishya, Xiaoyan Yang, Yi Hao, Varun Khurana, Dhananjay Pal. J Control Release. 219: 248–268.

[6] The toxins of William B. Coley and the Treatment of bone and soft-tissue sarcomas. (2006). McCarthy EF. Iowa Orthop J. 26: 154–158.

[7] https://www.cancer.gov/research/areas/treatment/immunotherapy-using-immu...