Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Aug 5;5(11):e1217374.
doi: 10.1080/2162402X.2016.1217374. eCollection 2016.

Immunotherapies targeting CD38 in Multiple Myeloma

Djordje Atanackovic  1 , Mary Steinbach  1 , Sabarinath Venniyil Radhakrishnan  1 , Tim Luetkens  1
Affiliations
Review

Immunotherapies targeting CD38 in Multiple Myeloma

Djordje Atanackovic et al. Oncoimmunology. .

Abstract

Recently, the monoclonal antibody daratumumab was approved as a single agent for the treatment of patients with relapsed/refractory Multiple Myeloma (MM). Daratumumab is an antibody targeting surface molecule CD38 on myeloma cells and the agent is already widely being used based on its good tolerability and proven efficacy. We believe, however, that the efficacy of this drug and other anti-CD38 monoclonal antibodies can be further improved by combining it with other types of immunotherapies. Furthermore, surface molecule CD38 can be used as a target for immunotherapies other than just naked monoclonal antibodies. In this report, we review the expression pattern of CD38 among normal tissues and in different types of plasma cell dyscrasias including their progenitor cells, minimal residual disease, and circulating tumor cells. We summarize the physiological role of CD38 as well as its role in the pathophysiology of MM and we present the most recent clinical trials using CD38 as a target. In addition, we highlight possible combination immunotherapies incorporating anti-CD38 monoclonal antibodies and we demonstrate alternative immunotherapeutic approaches targeting the same antigen such as CD38-specific chimeric antigen receptor (CAR) T cells.

Keywords: CAR T cells; CD38; immunotherapy; immunotoxins; monoclonal antibodies; multiple myeloma.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Different types of CD38-specific immunotherapies. The figure shows different ways to target the CD38 surface molecule expressed on myeloma cells. The myeloma antigen can be targeted by mAb, antibody-drug conjugates (ADC) or bispecific antibodies, CD38-specific T cells recognizing HLA/CD38 peptide complexes, and CD38-specific CAR T cells.
See this image and copyright information in PMC

References

    1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med 2011; 364(11):1046-60; PMID:21410373; http://dx.doi.org/10.1056/NEJMra1011442 - DOI - PubMed
    1. Cotner T, Mashimo H, Kung PC, Goldstein G, Strominger JL. Human T cell surface antigens bearing a structural relationship to HLA antigens. Proc Natl Acad Sci U S A 1981; 78(6):3858-62; PMID:6167992; http://dx.doi.org/10.1073/pnas.78.6.3858 - DOI - PMC - PubMed
    1. Terhorst C, van Agthoven A, LeClair K, Snow P, Reinherz E, Schlossman S. Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. Cell 1981; 23(3):771-80; PMID:7013988; http://dx.doi.org/10.1016/0092-8674(81)90441-4 - DOI - PubMed
    1. Mehta K, Shahid U, Malavasi F. Human CD38, a cell-surface protein with multiple functions. FASEB J 1996; 10(12):1408-17; PMID:8903511 - PubMed
    1. Nakagawara K, Mori M, Takasawa S, Nata K, Takamura T, Berlova A, Tohgo A, Karasawa T, Yonekura H, Takeuchi T et al.. Assignment of CD38, the gene encoding human leukocyte antigen CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase), to chromosome 4p15. Cytogenet Cell Genet 1995; 69(1-2):38-9; PMID:7835083; http://dx.doi.org/10.1159/000133933 - DOI - PubMed