Recently, several investment news media reported Moderna's cancer vaccine for Melanoma being closed to be approved by the FDA. Below is from Yahoo Finance reporting the recent progress Moderna made on its mRNA based cancer vaccine + Keytruda immunotherapy for advanced Melanoma. I will try to decipher the current status of cancer vaccines using the Moderna’ cancer vaccine as an example
Moderna is a pharmaceutical company who specializes in mRNA technology. The company was founded in 2010. The company was not making money until their mRNA based vaccine for COVID-19 was approved by FDA along with Pfizer/Biotech mRNA based vaccine. So, the Moderna cancer vaccine uses the knowhow they gained for COVD-19 vaccine.
Identify which antigens (proteins) of cancer cells will invoke a strong immune response.
Encapsulate DNA or mRNA for the specific antigen or antigens in a nano size lipid.
Inject into an arm many lipids or many viruses which contain DNA/mNRA of antigens of cancer
Lipids go inside cells of our body.
When lipids reach the cytoplasm area of a cell, it releases mNRA.
Enzyme called RIbosome reads mRNA and produces antigens.
When antigens go outside of the cell, our immune system recognizes antigens as pathogens and produces antibodies and T-cells.
And antibodies and T-cells circulate through blood vessels.
When a cancer cell arises which expresses the antigens which T-cells recognize, T-cells kill the cancer cell.
What is unique about the Moderna cancer vaccine is that antigens are obtained from cancer of a patient. So, they call the Moderna cancer vaccine “personalized cancer vaccine”. Also, because Moderna is an expert in mRNA based vaccine, Moderna claims that once they identify which antigens the vaccine should target, the personalized cancer vaccine can be made within a few months,
As any cancer drug development is financially risky, Moderna has chosen Merck as a partner for its cancer vaccine development. Merck invested $250 million worth shares in Moderna for its cancer vaccine development and Merk and Moderna split revenue from the sale of Cancer vaccine for Melanoma. The first cancer vaccine Moderna developed was the combination of Keytruda immunotherapy drug and Moderna cancer vaccine for Melanoma. This approach makes sense as even if the vaccine invokes immune responses against specific antigens of cancer cells, we know that cancer cells can evade T-cells by expressing PD-L1 immune checkpoint on cancer cells. Keytruda (PD-1 immune checkpoint inhibitor) lets T-cells ignore PD-1 immune checkpoint and go ahead to kill cancer cells regardless of PD-L1 being expressed on cancer cells.
Phase II of the clinical trial which compared Moderna Cancer Vaccine + Keytruda vs Keytruda alone showed 44% improvement in efficacy. The vaccine is given in
nine doses every 21 days
, in combination with one dose of Keytruda every 21 days up to 18 times.
The participants were patients with stage III or IV resectable cutaneous melanoma, which had metastasized to a lymph node, who were considered to have high risk of recurrence. They were eligible if following complete resection, they had no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases. Note that vaccine for bladder cancer is in a pipe lines for mRNA based cancer vaccine development by Moderna.
It is noted that a cancer vaccine is not to prevent cancer from arising but rather killing as cancer as soon as the cancer arises. This is in contrast to other vaccines including the vaccine for COVID-19. The vaccine for COVID-19 first prevents us from being infected with the virus by using antibodies produced by the vaccine as the first defense. Some virus still gets into cells in the lung, then T-cells attack virus infected lung cells to prevent further spreading of infection to lung cells. Cancer vaccines do not utilize antibodies. Cancer is the result of accumulation of mutations of multiple genes, i.e. in average 200 gene mutations in bladder cancers. As far as I know, there are no drugs (vaccine) to prevent genes from mutating. Though our body has its own mechanism to repair DNA damage, preventing abnormal cells from replicating, cancers have evolved to escape from those internal correction mechanisms. So, at present, cancer vaccines are to kill cancer cells as soon as they arise.
For a cancer vaccine to succeed, identifying which antigens expressed in cancer cells will give the best response from the patient's immune system against the antigens. I will explain it next.