CD38 Specific Neutra™ Antibody Products

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CD38, a type II transmembrane glycoprotein, exhibits non-lineage restriction and is involved in the synthesis and hydrolysis of cyclic adenosine 5'-diphosphate-ribose, serving as an intracellular calcium ion mobilizing messenger. The protein exhibits dual extracellular and intracellular functionalities, as indicated by the liberation of soluble protein and the internalization potential of membrane-anchored protein. CD38 consists of an N-terminal cytoplasmic tail, a solitary membrane-spanning segment, and a C-terminal extracellular domain containing four N-glycosylation sites.

Its Gene ID: 952, UniProtKB ID: P28907, and OMIM ID: 107270.

CD38 Involved in Adenosine Synthesized Pathways

CD38 is situated on both the plasma membrane and endoplasmic reticulum. It has the capability to synthesize two structurally distinct messengers, namely nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (cADPR), operating at both acidic and neutral pH levels. The breakdown of ADPR is facilitated by the cooperative action of CD203a/PC-1 and CD73, resulting in the generation of the immunosuppressive molecule. This characteristic underscores the role of CD38 in enabling tumor cells to evade immune system control.

Fig. 1 The CD38/NAADP/cADPR -signaling pathway. (Lee, et al., 2019) Fig.1 The CD38/NAADP/cADPR-signaling pathway.¹

Application of Anti-CD38 Antibodies in Disorders Treatment

CD38 plays a pivotal role in mediating the production of the immunosuppressive molecule adenosine, highlighting its involvement in enabling tumor cells to evade immune system control. The elevated and uniform expression of CD38 on malignant plasma cells, coupled with its relatively lower expression on normal lymphoid and myeloid cells as well as nonhematopoietic tissues, positions CD38 as a promising therapeutic target. Immunotherapeutic strategies targeting CD38 hold potential for combination with conventional therapies, enhancing overall efficacy.

Targeting CD38 monoclonal antibody in multiple myeloma has immunomodulatory potential

CD38 functions as an immune checkpoint molecule in human multiple myeloma (MM) cells. Treatment with anti-CD38 monoclonal antibodies (mAbs) reduces its levels, representing a therapeutic strategy to counteract adenosine suppressive mechanisms in MM. Combining anti-PD-1/PD-L1 treatment with anti-CD38 mAbs could potentially result in the expansion of T effector cells in the bone marrow of patients with MM. mAb immunotherapy targets the immune response to instigate a systemic anti-tumor effect. CD38 represents a valuable therapeutic target for mAbs, given its ability to hinder tumor growth through the induction of immune modulation or direct targeting of cells. mAbs also provide notable benefits, such as enhanced survival in diverse cancer types and the effective induction of enduring responses. For MM therapeutic strategy research, Creative Biolabs provides Recombinant Anti-CD38 Antibody (V3S-0622-YC78) and Anti-CD38 Neutralizing Antibody (V3S-0622-YC1298).

Fig. 2 Overview of anti-CD38 mAbs' mechanism of action on MM cells.²

Exploring CD38 as a therapeutic target in AL amyloidosis

Similar to MM, AL amyloidosis is a form of plasma cell dyscrasia sharing certain genetic aberrations and therapeutic strategies. CD38 emerges as a promising target in AL amyloidosis, and indeed, anti-CD38 monoclonal antibodies (mAbs) exhibit significant therapeutic potential. CD38 mAbs function as modulators, influencing the balance of immune cells, and as agents depleting plasma cells. The surface expression of CD38 on natural killer (NK) cells and B cells makes these cells potential targets for CD38 mAbs.

Fig. 3 Key effects of anti-CD38 antibodies on tumor targets and main functional effector cells. (Roccatello, et al., 2020) Fig.3 Key effects of anti-CD38 antibodies on tumor targets and main functional effector cells.³

Creative Biolabs provides an array of more than fifty anti-CD38 antibody products, applicable for research in therapies targeting MM, AL amyloidosis, cervical cancer, and other conditions. Furthermore, customization options are available for developing CD38-based bispecific antibodies.

REFERENCES

Lee, Hon Cheung, and Yong Juan Zhao. "Resolving the topological enigma in Ca2+ signaling by cyclic ADP-ribose and NAADP." Journal of Biological Chemistry 294.52 (2019): 19831-19843.
Morandi, Fabio, et al. "CD38: a target for immunotherapeutic approaches in multiple myeloma." Frontiers in immunology 9 (2018): 2722.
Roccatello, Dario, et al. "CD38 and anti-CD38 monoclonal antibodies in AL amyloidosis: targeting plasma cells and beyond." International Journal of Molecular Sciences 21.11 (2020): 4129.

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