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from a large Phase I dose expansion trial that have since modified using a TGF-beta antisense plasmid to block TGF-
been updated. beta secretion. TGF-beta inhibits T and B cell activation,
dendritic cell maturation and antigen presentation, as well
PD-L1 expressed on cancer cells can bind to PD-1 on nd natural killer (NK) and lymphokine activated (LAK)
activated T cells to suppress the immune system. activation. TGF-beta also induces immunosuppressive T
regulatory cells.
MPDL3280A is an IgG1 monoclonal antibody against PD-L1
that targets cancer cells expressing PD-L1, thus preventing In addition to the vaccines described above, there are
the interaction between PD-L1 and PD-1 expressed on several other types of vaccines that are currently being
activated T cells. It is also engineered to prevent antibody- evaluated in phase III studies. More effort is being invested
dependent cell-mediated cytotoxicity (ADCC) and into developing new vaccines and combining vaccines
complement mediated cytotoxicity in activated T cells that with other immunologic agents, chemotherapy, or targeted
may express PD-L1. Similarly, IgG1 monoclonal antibody agents. Advances in DNA and RNA sequencing as well as
MEDI4736 and IgG4 monoclonal BMS-936559 also target drug development may also ultimately enable the design
PD-L1. BMS-936559 is a fully human antibody that is an of personalized vaccines consisting of antigens uniquely
IgG1 monoclonal antibody to PDL1 with an engineered expressed by tumour cells from a specific patient.
Fc domain to eliminate MEDI4736 effector function (i.e.
complement mediated cytotoxicity and ADCC). BMS- CONCLUSION
936559 is a fully human IgG4 monoclonal antibody to
PDL1 which has been evaluated in a dose escalation phase Lung cancer is the leading cause of cancer-related mortality
I trial with expansion cohorts in NSCLC, melanoma, and in the United States and worldwide. More than 80% of lung
renal cell carcinoma. [24] cancer cases are classified as NSCLC. In the past decade,
there has been significant breakthrough in our understanding
Vaccination of the tumour biology of NSCLC. Signalling pathways that
Non-small cell lung cancers (NSCLCs) are characterized are vital for tumour growth have been identified and have
by several genetic alterations in neoantigens that can been effectively targeted pharmacologically. This article
potentially be recognized by the immune system as foreign. summarizes the implications of these advances for treating
Vaccination enhances the body’s exposure to such antigens lung cancer and highlights the ongoing work to improve
and immune cell priming. Randomized trials are currently clinical outcomes of this disease. Treatment of lung cancer
focusing on approaches that couple tumour antigens or has come a long way with greater use of molecular markers
cells with immune adjuvant agents; such approaches may and targets. Nonetheless, there is still much to be done to
enhance the antigen presenting cell response to the vaccine. help our fight against lung cancer.

One example is the melanoma associated antigen A3 Acknowledgments
(MAGE-A3) vaccine. The melanoma associated antigen Department of Pathology, Army Hospital Reseach and
A3 (MAGE-A3 gene family consists of “cancer germline” Referrral, New Delhi.
or “cancer testis” genes that are normally expressed only
on testicular germ cells and placental trophoblasts. Financial support and sponsorship
[25]
Several tumours also express MAGE-A3, including Nil.
30-50% of NSCLCs. The GSK1572932 vaccine is a
recombinant MAGE-A3 protein vaccine combined with the Conflicts of interest
immunological adjuvant AS15. There are no conflicts of interest.

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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ June 15, 2016 ¦