Posted on December 2nd, 2015
by David Hansen
In my last post, I explained the difference between a colloquially termed “fully human antibody” and the truly fully human antibody discovery platform that MabVax has at its disposal. When scientists refer to a fully human antibody, they are referring to an antibody created with human genes, but not necessarily one taken from an actual human patient. With MabVax’s HuMab 5B1 antibody (“5B1”) we are referring to an antibody produced by an actual human in response to a vaccine constructed to elicit an antibody response to a specific cancer antigen.
Recently, a series of successful studies were conducted on 5B1 and presented at the 2015 World Molecular Imaging Conference (WMIC) in September. These experiments showed the remarkable utility of this antibody and what it can potentially become.
We have known for quite a while about 5B1’s affinity for pancreatic cancer cells and therefore the possibility of its use as a pancreatic cancer imaging agent. 5B1 locks on to pancreatic cancer like a key in a lock via an antigen called CA 19-9. What was unknown was if the shedding of this cancer antigen into the blood would throw off diagnostic scans.
Thanks to data presented by Dr. Jacob Houghton at the conference, we now have evidence that this hurdle can mostly be overcome. To bypass the problem, small amounts of unlabeled 5B1 (meaning it won’t show up on an imaging scan) were first introduced in order to “soak up” excess antigen, shed from the cancer cells, floating around in the blood. That way, the labelled 5B1 would not be diverted from cancer cells to tag loose antigens that were not associated with the cancer itself.
Dr. Houghton was able to determine the variables needed to optimize PET images in accordance with the amount of antigen shedding. As a result, PET images from the labeled 5B1 consistently highlighted the cancer. We now know that antigen shedding is likely not be an insurmountable problem for 5B1 as an imaging agent, and that is a very important step forward.
If 5B1 can work as an imaging agent by carrying a radioactive label, then the next question would be could it potentially act therapeutically carrying radiometals specifically used to kill cancer cells. Dr. Ryan Lanning, who headed experiments using HuMab 5B1 as a , also presented at WMIC. Dr. Lanning’s experiments were very encouraging, and showed significant tumor killing capability, as well as, strong tumor localization – meaning potential toxicity was localized strictly to the tumor itself, and not surrounding tissues.
Dr. Jan-Phillip Meyer and Dr. Jacob Houghton presented research showing that HuMab 5B1 could potentially be linked with radioactive labels with much shorter half-lives. The objective being to reduce the amount of radioactivity a patient is exposed to during a PET imaging procedure. This is an important finding because it would give 5B1 a commercial advantage over imaging competitors. In this study the antibody was combined with a linker but not the PET radiolabel. The antibody and linker were administered first and attached to the pancreatic cancer cells. The short acting PET radiolabel was combined with a complimentary linker and administered separately later. The PET radiolabel plus linker then found the antibody plus linker in the live animal. The research showed that 5B1 could be used with these other radiolabeled small molecules as well. All images came out sharp, with good contrast between tumor and background even in the presence of shed antigen. The hope is that this approach would enable physicians to reduce radiation exposure in their patients making PET imagine even more useful.
Finally, Dr. Dalya Abdel-Atti presented research showing that HuMab 5B1 PET imaging produced high quality images in a mouse organoid model. An organoid model is taken from an actual pancreatic tumor and allowed to propagate into something resembling an actual pancreas cancer. This kind of model more faithfully replicates metastatic cancer in patients and is more predictive of results in actual patients. Investigators from our partner believe this is the very first time successful PET imaging has been achieved in this kind of model of pancreatic cancer.
Overall, the results presented at WMIC are not just encouraging, but bring us that much more insight as we continue to develop HuMab 5B1 as both a therapeutic and diagnostic product. I look forward to keeping you updated as we progress. We plan to submit two INDs for HuMab 5B1 as an imaging agent and therapeutic by the end of this year and look forward to commencing human clinical trials in 2016.
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