An Immunotheranostic Antibody for the Detection and Eradication of Metastatic Prostate Cancer: a Proof-of-Concept Study in Nonhuman Primates
Abstract
Rationale: We have developed a new and exciting generation of antibody-based drugs that recognize a very specific target inside prostate cancer, called kallikreins or KLKs. One of these, KLK2, is specifically produced by prostate cancer cells and is the main target of our drug. Once injected, these drugs can find cancer cells in the prostate or nearly anywhere they go if the cancer has spread. By attaching a radioactive atom to the drug, we can track it inside the body and take snapshots of it as it homes in on its target. These pictures also allow us to diagnose the location and extent of disease. When needed, we can equip the very same antibody drug with a toxic radioactive atom that attacks the cancer cells specifically, effectively becoming a precision-guided warhead that can kill malignant cells flagged with KLK2. Objective: We have shown that our antibody drugs can be used to diagnose and cure prostate cancer in mice. Now, as a final step prior to testing them in humans, we want to assess the safety and efficacy in monkeys, since they are much more like humans and produce organ-specific prostate kallikreins, unlike mice. Aims: The first aim of this project is to evaluate the ability of our drugs to precisely image and target the prostate in monkeys. Based on these images, we will calculate the trajectory of the antibodies and optimize the dose of antibodies to carry toxic radionuclides. In our second aim, we will study the effects of different amounts of toxic radionuclides to be carried by the antibodies and validate the biological effects on the prostate, as well as potential bystander organs. What types of patients will this help? No effective treatment for locally advanced or disseminated late-stage prostate cancer currently exists and, staggeringly, more than 29,000 American men succumb to the disease each year. Diagnosis of metastases directly excludes patients from curatively intended surgery or irradiation. Our antibody-based treatment strategy has the potential to cure these patients. How will it help these patients? Attaching radioactive agents to the antibody enables the ability to locate tumors, as well as to measure their sensitivity to certain drugs. The use of these antibodies would result in earlier diagnosis of metastasis, less invasive treatment, and greater hope to those suffering with the more advanced stages of the disease. Clinical applications and risks/benefits: Unlike radiation treatment or chemotherapy, these drugs offer the possibility of exclusively treating prostate cancer cells without destroying healthy neighboring cells; as such, they represent a potential improvement in prostate cancer diagnosis, staging, and treatment. They are also ready for human testing. Furthermore, because we can choose which radioactive atom to affix to the drug, we have exquisite control over the lethality of the drug, and thus its risk to patients; i.e., while some are relatively non-toxic and very useful for imaging, as they can identify the location of tumors, others are carefully chosen for treatment and are much more powerful and damaging. Expected time to achieve patient outcomes: We have streamlined and optimized the design of our antibody drug so that it works better in people and have begun planning a clinical trial. The proposed study will provide invaluable information regarding the efficacy and safety of the drug in patients with prostate cancer. Assuming a clinical trial commences soon after the completion of this work, we would definitively know whether the drug is working within 4-6 months; if it represents a significant improvement in the current standard of care, this would become apparent after 1-2 years. Likely impact of study on central problem in prostate cancer: We know that antibody-based drugs are very specific and often result in fewer side effects than traditional treatments. That being said, we are hopeful that these KLK2-targeted radioactive
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810223
Entities
People
- Hans David Ulmert
Organizations
- Memorial Sloan Kettering Cancer Center
- United States Army