Immunotherapy: The Future of Lung Cancer Treatment?

Lung cancer is one of the most common types of cancer worldwide and accounts for around one fifth of cancer-related deaths. Lung cancer is a more common cause of death among cancer patients than breast, colon and prostate cancer combined.

Unfortunately, by the time lung cancer is diagnosed, it has usually progressed to the later stages of disease and is unlikely to respond well to conventional treatments such as surgery, chemotherapy and radiotherapy.

Lung cancer is one of the main forms of cancer for which immune-based therapies are being developed. A number of patients with late stage lung cancer have benefited from this form of treatment and experienced remission and prolonged survival. The immunotherapies currently being developed for lung cancer can be divided into four main groups and these are described in more detail below.

Checkpoint inhibitors

Checkpoint inhibitors represent a promising new approach to treating lung cancer. They “take the brakes” off the immune system, enabling it to mount a more effective and more powerful attack against cancer cells. Currently, there are several different types of checkpoint inhibitors being used that target different immune cell checkpoints or “brakes”.

One of the main braking molecules that is targeted by checkpoint inhibitors is PD-1, which is present on certain immune cells. A phase III trial showed that the checkpoint inhibitor nivolumab increased the survival of patients with advanced squamous non-small cell lung cancer (NSCLC) by an average of 3.2 months, compared with patients who received chemotherapy.

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  • Another phase III trial showed that the drug also increased survival in patients with non-squamous NSCLC by an average of 2.8 months, compared with patients who received chemotherapy. In 2015, the Food and Drug Administration approved the use of nivolumab for the treatment of both squamous and non-squamous NSCLC.

    Monoclonal Antibodies

    These are molecules produced in the laboratory that specifically target the antigens present on tumors. Two monoclonal antibodies that have been approved by the FDA for the treatment of lung cancer are bevacizumab and ramucurimab. Some of the monoclonal antibodies that are currently being tested as a treatment for lung cancer in clinical trials include the following:

    • Bavituximab
    • Patritumab
    • Rilotumumab
    • Cetuximab
    • IMMU-132
    • Demcizumab

    Therapeutic cancer vaccination

    This is an immunotherapy that primes the immune system to generate an immune response against tumor-specific antigens. The immune system produces CD4+ T-helper cells, CD8+ cytotoxic T-lymphocytes, and antigen-specific antibodies against antigens associated with tumors.

    Among these antigens are p53, which is mutated in around half of all lung cancers; MAGE-3, which is present in over 40% of lung cancers and NY-ESO-1, which occurs in 30% of lung cancers.

    Therapeutic vaccines that are currently being studied in clinical trials for the treatment of stage III NSCLC include:

    • Tergenpumatucel-L
    • DRibbles
    • GV1001

    Adoptive Cell Therapy

    A fourth immunotherapy approach to treating lung cancer is the use of adoptive cell therapy. Here, T cells are taken from a patient and genetically or chemically modified to improve their activity. The T cells are then introduced back into the patient, with the aim of improving their anti-cancer response.

    A number of adoptive cell therapies are currently being tested in clinical trials including trials of T cells that have been modified to recognize the tumor specific antigens NY-ESO-1; VEGFR2 and MAGE-A3.

    Sources

    • www.cancerresearch.org/.../lung-cancer
    • http://www.medscape.com/viewarticle/818715_3

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