On October 21, 2015 MabVax Therapeutics Holdings, Inc. (OTCQB: MBVX) a clinical-stage oncology drug development company reported its antibody, HuMab 5B1 was featured in five separate presentations at the recently held World Molecular Imaging Congress (WMIC) in September (Press release, MabVax, OCT 21, 2015, View Source [SID:1234507749]). The presentations were made by investigators from the Department of Radiology at Memorial Sloan Kettering Cancer Center (MSK) describing the novel use of MabVax’s lead antibody as a PET imaging agent and a radioimmunotherapy agent targeting pancreatic cancer.
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Following is a summary of the key points from the presentations;
Jacob Houghton, Ph.D. presented data demonstrating that the HuMab 5B1 antibody based PET imaging agent could be useful even in the context of shed antigen. Most pancreatic cancer patients shed an antigen called CA 19-9, which is a validated biomarker for pancreatic cancer. This same target is overexpressed on the surface of pancreatic cancer cells in more than 80% of patients and is the target for the HuMab 5B1 antibody. In animal models of pancreatic cancer, the experiments examined adding small amounts of HuMab 5B1 antibody not labeled with radiotracer to "soak up" excess circulating antigen. By varying the amount of unlabeled antibody and the time before injection of the HuMab 5B1 PET agent, Dr. Houghton was able to determine the variables required to optimize PET images. However, regardless of time of administration or amount of non-radiotracer antibody administered, images consistently illuminated the cancer.
Ryan Lanning, M.D., Ph.D. presented the results of experiments using the HuMab 5B1 antibody as a radioimmunotherapy agent against pancreatic cancer. Dr. Lanning conjugated the HuMab 5B1 antibody to two different and commonly used radiometals in radioimmunotherapy and tested them in animal models of pancreatic cancer. He varied the dose administered as well as examined the impact of combining the 5B1 radioimmunotherapy agent with chemotherapy. Both the radioimmunotherapy conjugates demonstrated significant tumor toxicity and excellent tumor localization potentially minimizing toxic adverse effects. Subsequent to administration of the radioimmunotherapy agent, follow-on administration of the HuMab 5B1 PET product continued to demonstrate sustained tumor selectivity allowing for administration of additional antibody based therapeutic or diagnostic agents.
Jan-Philip Meyer, Ph.D. and Jacob Houghton, Ph.D. each presented research using pretargeting as an effective way to combine the favorable pharmaocokinetic properties of radiolabeled small molecules with short half-lives with the affinity and specificity of the HuMab 5B1 antibody. Using different linking technologies and different radiotracers each investigator reported very good PET images with very favorable tumor-to-background activity ratios. The objective of both sets of experiments was to demonstrate methods that could be used to reduce the exposure of patients to excess radiation when undergoing PET imaging. Both investigators were able to achieve that objective even in the presence of shed antigen.
Dalya Abdel-Atti presented research showing that using a HuMab 5B1 based PET imaging agent produced high-quality images in a pancreatic cancer murine organoid model even in the presence of shed antigen. A central drawback of many animal models of disease is that they aren’t always predictive of the results obtained in actual patients. The murine organoid model is a newly developed model that more faithfully replicates metastatic pancreatic cancer in patients. The investigators at MSK believe that this is the first time PET imaging has been successfully performed in a murine organoid model of pancreatic cancer.
David Hansen, CEO of MabVax commented "These investigators need to be commended for the pioneering work they presented and the important steps forward they have made in building capabilities to diagnose and treat a very difficult cancer. MabVax is grateful to Jason S. Lewis, Ph.D. and his team for their pioneering work done with our HuMab 5B1 antibody. All of these results are helpful steps forward in advancing the collective knowledge of this devastating cancer and provide valuable insights for MabVax as we continue to develop HuMab 5B1 as both a therapeutic and diagnostic product."
About HuMab 5B1
The fully human antibody HuMab 5B1 was recovered from patients undergoing cancer vaccine treatment at Memorial Sloan Kettering Cancer Center. The HuMab 5B1 has demonstrated high specificity, affinity, and lack of cross-reactivity with similar antigens. The antibody has also shown potent cancer cell killing capacity and efficacy in animal models of pancreatic, colon, and small cell lung cancers. Ongoing toxicology results continue to demonstrate an acceptable profile in acute and repeat dose studies in animals. MabVax plans to initiate two complementary Phase I clinical trials in the first quarter of 2016. One clinical trial is aimed at determining the safety and potential utility of HuMab 5B1 as a therapeutic agent in subjects with metastatic pancreatic cancer. The second clinical trial is aimed at demonstrating the utility of 89Zr-HuMab 5B1, the Company’s radio-labeled HuMab 5B1 antibody, as a next-generation PET imaging agent for the diagnosis, staging, and management of pancreatic cancer.