A Novel Antibody-Based Therapy Against Multiple Myeloma
Abstract
Multiple myeloma is a cancer of a type of white blood cell known as “plasma cells.” The myeloma cells grow in bone marrow, soft tissue found in the center of bones, destroying the surrounding bone and causing decreased levels of red blood cells (anemia), recurrent infections, and pain, among other symptoms, resulting in significant sickness (morbidity). Multiple myeloma is the second most common blood cancer in the United States, and its incidence has been increasing, presumably due to aging of the population. Apart from age, another risk factor is race, as African Americans show the highest incidence and mortality when compared to other racial groups. In addition, military personnel and Veterans are disproportionately affected by MM when compared to the general population. Although new therapies, including antibodies, have improved survival of patients affected with multiple myeloma, the disease remains incurable. The Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Topic Area that this project addresses is “blood cancers,” in our case focusing on multiple myeloma as a particularly relevant disease for members of the military. This project aims to develop a new therapeutic antibody against multiple myeloma. Although other approved antibodies against cancer in the clinic are of a class known as “IgG,” our project is focused on the development of a new antibody of the “IgE” class. Although, IgE antibodies are known for their role in allergic reactions, they also have several unique properties that make them attractive to test as a potential cancer therapy, including for multiple myeloma. The proposed IgE antibody will be specific for a molecule expressed on the surface of myeloma cells. This antimyeloma IgE would act as a “magic bullet” targeting multiple myeloma tumors and, in so doing, create an acute inflammatory “allergic like” response, which would result in tumor destruction. In addition, the anti-myeloma IgE will be able to “teach” the patient’s immune system to learn that myeloma cells are “foreign” and should be destroyed. Thus, the proposed IgE is a novel and rational approach aimed to trigger a multi-pronged attack against myeloma cells reducing the morbidity and mortality of multiple myeloma. Since we aim to develop a novel and effective antibody therapy against MM, the FY19 PRCRP Military Health Focus Area addressed is: “Gaps in cancer prevention, early detection/diagnosis, prognosis, treatment, and/or survivorship that may affect the general population but have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries.” Although our project is focused developing a new IgE antibody targeting a particular myeloma molecule (marker), the proof-of-principle obtained in this project would pave the way to develop other IgE antibodies targeting different myeloma markers. Importantly, the IgE treatment can be used as a therapy alone or in combination with other therapies, including antibodies of the IgG class, maximizing the possibility of finding a cure. In fact, the use of the IgG and IgE antibodies is not mutually exclusive, since each class of antibody has different but complementary roles in immunity. Moreover, since the myeloma molecule that we are targeting has also been detected in other blood cancers, such leukemias and lymphomas, which are also malignancies of higher incidence in military personnel compared to the general population, our studies are expected to have a broader impact that will extend beyond multiple myeloma. In summary, the proposed research will advance the cancer treatment options to increase mission readiness and quality of life by decreasing the burden of cancer on Service members, their families, and the American public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010455
Entities
People
- Manuel Penichet
Organizations
- United States Army
- University of California, Los Angeles