How to Improve Cancer Vaccines Research Efficiently

Posted by Candy Swift on May 30th, 2019

Cancer vaccine uses the tumor cell-associated antigen to awaken the body's immune system against cancer. The most popular cancer vaccine programs now need to first discover and confirm tumor cell-associated antigens. There are hundreds of these antigens. Almost half of the ongoing clinical trials involve one or more antigens. Unfortunately, these antigens only stimulate a weak immune system response. If a large number of T cells against tumor cell-associated antigens are to be produced, not only a suitable antigen but also a combination of various stimulation signals is required; without these signals, T cell inactivation and peripheral tolerance occur. Therefore, the new antigen test uses a variety of immunostimulatory molecules to increase feedback from the immune system.

What are cancer antigens?

Cancer antigens are generally divided into common antigens and specific antigens, which may develop into powerful cancer vaccine adjuvant. Common antigens can be found on many cancers, and specific antigens are mutations caused by physical or chemical carcinogens, which exhibit different characteristics on different tumors. In one vaccine manufacturing method, the vaccine contains intact tumor cells, however, this vaccine is inefficient in inducing an immune response. Another approach is to have a specific antigen in the vaccine that reduces the risk of developing an autoimmune disease, but cancer cells can escape from the vaccine by simply reducing the performance of the antigen. Epitope transfer, an immune process, is capable of overcoming the weakness. Although only a single antigen is injected, the immune system can fight against many different antigens by B cells. For instance, Hsp70 plays a much important role in antigen presentation including tumor antigen presentation, which has been considered a greatly effective cancer vaccine adjuvant.

Clinical trials of cancer vaccine development

In Phase 3 clinical trials of follicular lymphoma, the investigators reported that BiovaxID donors had an average life expectancy of 44.2 months compared to 30.6 months in the control group. On April 14, 2009, Dendreon announced a prostate cancer vaccine, Sipuleucel-T, which significantly increased patient survival after Phase 3 clinical trials. This was approved by the Food and Drug Administration for advanced prostate cancer treatment on April 10, 2010. On April 8, 2008, New York company Antigenics announced that they have obtained a license for a cancer treatment vaccine in Russia, which is the world's first approved cancer immunotherapy. Oncophage, a cancer vaccine in the Phase 3 clinical trial, increased the survival rate of patients without recurrence by about over a year. The approved sample was a group of kidney cancer patients with a moderate risk of recurrence. However, it is still waiting for approval from the US and the European Union, and before that, it has to undergo FDA testing. The third phase of clinical interim results showed that the anti-cancer effect of talimogene laherparepvec on melanoma was more significant than the injection of GM-CSF alone.

Suggestions for vaccine research

The treatment of vaccines is supposed to lower the disease burden, which requires a random Phase 2 clinical trial to ensure the power of the Phase 3 trial large enough (1-beta value), and avoid setting adjuvant values as the control value in a randomized trial. Vaccines aim to replace standard treatment procedures and create a good immunotherapy but adjuvants may have a low clinical effect to cause false negative results in the test.  Meanwhile, adjustments should be made based on clinical data rather than the degree of immune response in the vaccines treatment. The time-event relation is valuable for clinical diagnosis. At last, the vaccine-related production or testing should be invested at an early stage and the method should be designed to regulate the intensity of the reaction from the beginning of vaccine manufacturing.

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