Gene and Cell Therapies: A Breath of Fresh Air for Lung Cancer Treatment?

November is Lung Cancer Awareness month, a disease which the American Cancer Society predicts we will see 235,760 new cases of and 131,880 deaths in the U.S. in 2021. Gene and cell therapies are a beacon of hope in this regard, showing remarkable and highly encouraging results in the treatment of this disease.  

The Facts

Lung cancer (LC) is the leading cause of cancer deaths worldwide. Clinically, LC is divided into two major categories: 1) small cell lung cancer, which occurs almost exclusively in heavy smokers, and 2) non-small cell lung cancer, a term which references several cancer subtypes including adenocarcinoma and squamous cell carcinoma, for example.

There are several risk factors which can influence your chances of developing lung cancer which include smoking and second-hand smoke inhalation, exposure to carcinogens such as asbestos, and other factors that can’t be controlled such as family history. Find out more here about how smoking can increase your chance of developing cancer.

Symptoms of Lung Cancer

A deadly feature of LC is that the signs and symptoms of disease typically only occur when the illness is advanced. Some signs of LC may include the following:

• A persistent new cough
• Coughing up blood
• Chest pain
• Dyspnea (Shortness of breath)
• Random weight loss.
• Headache

Current Treatments

The treatments offered for LC vary depending on the type you have, how advanced the disease is, and your overall health.

Non-small-cell LC has a variety of treatment options. If the tumour is contained to one lung and the patient is in good general health then surgery can be performed to remove the cancer and chemotherapy can potentially follow surgery. If surgery is not an option, then radiotherapy can be used to destroy the cancer cells, again potentially followed by chemotherapy.

Small-cell LC is typically treated with chemotherapy with or without radiotherapy, targeted drug therapy, and immunotherapy. Surgery is not used to treat this cancer as it is often the case that it has already spread to other parts of the body.

Gene and Cell Therapy and Lung Cancer

Gene and cell therapies represent an exciting option for the treatment and prevention of LC. Consequently, there are currently 146 active and recruiting clinical trials involving gene therapies for LC and an astounding 1,833 trials involving cell therapies. This highlights the wealth of fantastic research and advances currently being explored. Gene therapies can work to correct the genetic defects which have given rise to the cancer whereas most cell therapy research looks at the delivery of immune cells with the goal of eliminating the cancer cells.

With regards to gene therapy, there are many papers that explore the genetics of LC, such as this paper which beautifully reviews the use of CRISPR-Cas9 in LC. This paper published in Acta Biomaterialia in 2020 describes a combination therapy approach to deliver a drug, gene therapy, and photothermal agent for the targeting of non-small cell lung cancer. The authors used a chitosan polymer agent to create nanocomplexes of these therapies and the study showed excellent potential in the suppression of EGFR-mutated non-small cell LC.

Cell therapy is seeing many exciting leaps towards advanced treatments for LC. The use of CAR-T cells has potential to recognize and kill LC cells. The use of CAR-T cell therapy sees T cells being extracted from the blood of a patient and engineered ex vivo to express chimeric antigen receptors (CAR), in theory allowing them to target cancer specific antigens once reintroduced into the patient. CAR-T cell therapy has shown some fantastc clinical efficacy in a variety of cancers such a lymphoma and multiple myeloma, and so could be of advantage in LC; however, more research and trials are needed in order to improve the use of these therapies on solid-tumours like LC as there are limitations of immune cell infiltration and T cell exhaustion.

Overall, it is clear from clinical work and the literature discussed that gene and cell therapy offers a lot of potential in the treatment of LC. The current treatment options, which include drugs, radiotherapy, and surgical intervention options, have varying degrees of efficacy. Therefore, it is imperative that new generation therapeutics are developed, and thankfully it is evident that major leaps in this regard are being made.  

Dr. Mulholland is the Lee Placito Research Fellow and Junior Research Fellow (Somerville College) at the University of Oxford. He is a member of the ASGCT Communications Committee.