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Cancer is the second leading cause of death, responsible for 9.6 million deaths globally in 2018 according to the World Health Organization (WHO). Despite years of effort dedicated to improving outcomes, the incidence of cancer is expected to double by 2035. This year, oncology costs to worldwide health systems will exceed $150 billion.

Trends in treatment

Scientists are currently focusing on the human body’s own immune system which is ideally suited to fight disease. To eliminate or control cancer progression, researchers are looking toward immunotherapy techniques. Yet, current limitations and uncertainties prevent immunotherapies from reaching millions of cancer patients.

Several questions need to be addressed by the immunotherapy industry. Among them are the following:

  1. How do we detect antigens to improve adoptive cell transfer (ACT) therapies?
  2. What is the best therapy to harness the power of immune cells, Chimeric Antigen Receptor (CAR) T-cells or gene-modified T-cell Receptors (TCR)?

Chimeric Antigen Receptor (CAR) T-cell therapies and gene–modified T-cell Receptor (TCR) therapies are the two classes of genetically enhanced T-cells. CAR T-cells are T-cells collected from patients and genetically modified to destroy cancer cells. These tumor targeting T-cells are grown in the laboratory for two to three weeks before being infused back into the patient. The first two CAR T-cell therapies (Kymriah and Yescarta) were approved by the FDA in 2017 and by the European Medicines Agency in 2018.

Recently, there has been interest in engineering conventional TCRs, since they are able to recognize a larger array of potential antigens when compared with CARs. An alternate approach is to avoid adoptive cell therapies that utilize circulating T-cells from the blood and instead use TILs which have zero toxicity, since they are sourced from the patient and not re-engineered. Under consideration are several approaches for creating new CAR and TCR constructs, including the unmasking of antigens already present on or within tumors/cancer cells as well as enriching T-cells “trained” to detect certain antigens. In either case, it is important to understand which antigens are derived from viruses or tumors and which ones may be recognized by T-cells.

Navigating uncertainties

The future looks ambitious, but is still undefined. To achieve success, the pharmaceutical industry will need to address how to scale up immunotherapy production without compromising patient safety. This will require a more concerted effort to control manufacturing processes. Adopting good laboratory/manufacturing practices (GMP) will be crucial. Finally and perhaps most importantly, treatment costs and access will need to be managed carefully to ensure accessibility for all who need these life saving therapies.

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