Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma

• Type of Material: Article
• Authors: James Ackley, Emory University; Miguel Armenta Ochoa, Georgia Institute of Technology; Delta Ghoshal, Georgia Institute of Technology; Krishnendu Roy, Emory University; Sagar Lonial, Emory University; Lawrence Boise, Emory University
• Language: English
• Date: 2021-10-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cancers13194787
• Title of Journal or Parent Work: CANCERS
• Volume: 13
• Issue: 19
• Grant/Funding Information: The authors have received relevant funding from the Riney Family Foundation (L.H.B., S.L.), the Leukemia and Lymphoma Society (L.H.B., S.L.), the NSF Graduate Research Fellowship Program (D.G.), and the NIH [T32] (MAO} along with funding from affiliations listed.
• Keywords: ADC; ENGINEERED T-CELLS; IMiD; MONOCLONAL-ANTIBODIES; DARATUMUMAB MONOTHERAPY; vaccine; immunotherapy; THERAPY; BELANTAMAB MAFODOTIN; IMMUNOMODULATORY DRUGS; multiple myeloma; LENALIDOMIDE; Life Sciences & Biomedicine; bi-specific antibody; CAR-T; CHIMERIC ANTIGEN RECEPTOR; OPEN-LABEL; Science & Technology; Oncology; antibody; TERM-FOLLOW-UP
• Research Categories: Health Sciences, Oncology

Abstract

Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on‐target off‐tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while re-ducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR‐T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR‐T activation and provide protection from a suppressive immune mi-croenvironment. This review will first cover in‐class breakthrough therapies for each of these cate-gories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.