This transcript has been edited for clarity.
Hello. I’m David Kerr, Professor of Cancer Medicine at the University of Oxford. I have a lifelong interest in seeking to better understand biology, genetics, and ultimately the treatment of disease. colorectal cancer.
I invite us all to pause for a moment and be awed and amazed by the incredible advances in modern medicine.Stop for a moment, think together, and let me walk with you as I guide you. Protocols I was considering for treating patients with Lynch syndrome.
Lynch syndrome is the most common hereditary colon cancer syndrome. This is caused by a germline mutation in one of her four mismatch repair genes, affecting one in about 300 people in the population. In the most extreme cases, patients with Lynch syndrome have a lifetime risk, with 80% of these patients developing colorectal cancer. That’s a very important issue.
Over 20 years ago, I served on the Clinical Trials Advisory Committee with my great friend John Byrne, who did some really great work early on.he saw The impact of dietary starch and aspirin in trying to prevent the development of colorectal cancer in patients with genetic abnormalities and Lynch syndrome.. More than 20 years ago, we discovered starch and aspirin Attempts to prevent colorectal cancer from occurring.
A protocol I’ve been looking at recently, thankfully, looks at a combination of a recombinant trivalent adeno-5 vaccine and an interleukin-15 superagonist to act as an immunizer. stimulation. I mean, what? This is unusual. This is a very beautifully engineered, replication-defective adenovirus from the common cold.
Adenoviruses are designed for repeated administration. One of the early problems when we had our own gene therapy program was that antibodies against the therapeutic virus were generated very quickly and neutralized it. This antibody can be administered four, five, or six times without causing serious immune interference. This allows the administration of trivalent vaccines.
Adenoviruses incorporate antigens such as CEA (carcinoembryonic antigen) that have been fine-tuned to become superantigens. Therefore, it is more likely to be recognized by the immune system. MUC1 is a well-known tumor-associated antigen. This is a glycoprotein that has been well characterized in the literature for many years.
There are also clever homologues of brachyury that function as T-cell stimulators. This is also a transcription factor that has been modified to enhance T cell responses. In addition to that, there are very sophisticated constructs of IL-15 superagonists that are also expected to enhance T-cell responses, particularly around memory.
This is a great try.I was given a link to clinicaltrials.gov Let’s take a look at the protocol. We have great researchers and great centers, and this is a very smart randomized phase 2 trial design.
Thankfully, we’ve spent 20 years moving from starch and aspirin to this incredibly sophisticated approach to vaccinating people with Lynch syndrome. Its purpose is to prevent the development of colorectal cancer. If it is hereditary, if colorectal cancer cells appear, pre-vaccination should have been done using a very logical tumor antigen.
Modern medicine! There’s no doubt that it works. We have some very good preliminary data, preclinical clinical safety data, etc.
I was truly amazed at the sophistication of the approach and must wish the investigators all the best. Let’s take a look at the protocol. It’s science fiction made real. Please tell me what you think about it. If you have any comments or anything you want to say, please let me know.
For now, Medscapers, Ahoy. thank you.