CD38 (ADPRC1) CAR Chimeric Antigen Receptor (CAR): A Comprehensive Guide and Our Service & Product Introduction

CD38 (ADPRC1, ADP-Ribosyl Cyclase 1) is a key tumor-associated antigen (TAA) and a promising target for chimeric antigen receptor (CAR)-based immunotherapy. RGBiotech is committed to providing high-quality CD38 (ADPRC1) CAR expression plasmid vectors and professional custom vector construction services, supporting researchers and biopharmaceutical enterprises in accelerating the development of CAR-T/CAR-NK therapies for hematological malignancies and solid tumors. If you are interested in our CD38 (ADPRC1) CAR expression plasmid vectors or custom services, or have any questions about CD38 CAR research, please feel free to contact us at admin@rgbiotech.com. Our professional team will provide you with high-quality products and services, helping you accelerate the progress of your research and development.

Our CD38 (ADPRC1) CAR Expression Plasmid Vector Products and Custom Services

RGBiotech provides a full range of CD38 (ADPRC1) CAR expression plasmid vectors, covering 1st to 5th generation CARs, with diverse vector backbones and rich functional modifications, to meet the needs of different research stages (in vitro experiments, in vivo animal models, preclinical trials). At the same time, we provide professional custom plasmid vector construction services, tailoring personalized solutions according to your research needs, accelerating your research progress.

RGBiotech provides CD38 (ADPRC1) CAR expression plasmid vectors covering all generations (1st to 5th), meeting different research needs and application scenarios.
1) 1st Generation CD38 CAR: Only contains the CD3ζ intracellular signal domain. It can mediate the activation of T cells and kill CD38-positive tumor cells, but lacks co-stimulatory signals, resulting in weak T cell proliferation ability, short survival time, and limited anti-tumor efficacy.
2) 2nd Generation CD38 CAR: Adds one co-stimulatory domain (CD28 or 4-1BB) based on the 1st generation. CD28 co-stimulation enhances T cell activation and proliferation, while 4-1BB co-stimulation improves T cell persistence and memory formation, significantly enhancing anti-tumor efficacy. It is the most widely used generation in current research and clinical trials.
3) 3rd Generation CD38 CAR: Contains two co-stimulatory domains (e.g., CD28+4-1BB, CD28+OX40, 4-1BB+OX40). It integrates the advantages of different co-stimulatory signals, further enhancing T cell activation, proliferation, persistence, and anti-tumor activity, and is suitable for the treatment of refractory and relapsed tumors.
4) 4th Generation CD38 CAR (Armored CAR): On the basis of the 3rd generation, it is engineered to express cytokines (IL-12, IL-15, IL-18) or immune checkpoint inhibitors (PD-1 scFv, CTLA-4 scFv). It can remodel the tumor microenvironment, overcome immune suppression, and enhance the anti-tumor effect of CAR-T cells, especially suitable for solid tumors with complex microenvironments.
5) 5th Generation CD38 CAR (Universal CAR): Optimized for off-the-shelf therapy, including allogeneic CAR-T cells (edited by CRISPR/Cas9 to knock out CD38, TCR, or HLA genes) and universal CAR structures (e.g., bispecific CAR, switchable CAR). It solves the problem of donor shortage and reduces the risk of graft-versus-host disease (GVHD), accelerating the clinical transformation of CAR therapy.

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Introduction of CD38 (ADPRC1)

CD38, also known as ADP-Ribosyl Cyclase 1 (ADPRC1), is encoded by the CD38 gene (NCBI Gene ID: 952; Uniprot ID: P28907). Located on human chromosome 4 (4p15), the CD38 gene spans approximately 20 kb, contains 8 exons, and encodes a 300-amino-acid transmembrane glycoprotein. As a highly conserved gene across species, CD38 is widely expressed in vertebrates, with its sequence and functional domains highly conserved, laying a solid foundation for cross-species research and preclinical trials.

CD38 (ADPRC1) protein is a type II transmembrane glycoprotein with a molecular weight of approximately 45 kDa, consisting of three functional domains: 1) Cytoplasmic N-terminal domain (1-21 amino acids): Short and highly conserved, involved in intracellular signal transduction and protein-protein interactions. 2) Transmembrane domain (22-44 amino acids): A single α-helical transmembrane segment that anchors the protein to the cell membrane, ensuring its surface expression. 3) Extracellular C-terminal domain (45-300 amino acids): The largest functional domain, containing the active site of ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase, and serving as the binding site for CAR single-chain variable fragments (scFv). The extracellular domain of CD38 is highly glycosylated, which is crucial for its antigenicity and binding ability to CARs. This structural feature also provides a specific target for the design of anti-CD38 scFv in CAR construction.

CD38 (ADPRC1) is a multifunctional protein with dual roles as an enzyme and a receptor, participating in multiple physiological and pathological processes.
1) Enzymatic activity: It acts as an ADP-ribosyl cyclase and cyclic ADP-ribose (cADPR) hydrolase, catalyzing the synthesis and hydrolysis of cADPR, a key second messenger that regulates intracellular calcium ion (Ca²⁺) homeostasis, thereby affecting cell proliferation, differentiation, and apoptosis.
2) Receptor function: As a cell surface receptor, CD38 interacts with ligands such as CD31 (PECAM-1), mediating cell adhesion, immune cell recruitment, and intercellular signal transduction. It is also involved in the activation and differentiation of immune cells (e.g., T cells, B cells, NK cells).
3) Regulatory role in immune response: CD38 is a marker of immune cell activation; its expression is upregulated by cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor (TNF), and it participates in the regulation of innate and adaptive immune responses, as well as immune escape of tumor cells.

CD38 (ADPRC1) has a broad but uneven tissue distribution, with distinct expression patterns in normal and tumor tissues.
1) Normal tissues: Low to moderate expression in hematopoietic cells (plasma cells, B cells, T cells, NK cells, monocytes, granulocytes), as well as in some non-hematopoietic tissues (bronchial epithelial cells, colon, seminal vesicles, spleen, mesenteric lymph nodes, and brain). The low expression in normal tissues provides a favorable safety window for CD38-targeted immunotherapy.
2) Tumor tissues: High and specific expression in a variety of hematological malignancies and solid tumors, including multiple myeloma (MM, almost 100% of primary and relapsed cases), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), as well as solid tumors such as ovarian cancer, lung cancer, and pancreatic cancer. This high expression makes CD38 an ideal target for CAR-T/CAR-NK therapy.

CD38 (ADPRC1) is closely associated with the occurrence, development, and prognosis of multiple diseases.
1) Hematological malignancies: Multiple myeloma (the most closely related disease), acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, etc. CD38 expression is positively correlated with tumor progression, drug resistance, and poor prognosis in these diseases.
2) Solid tumors: Ovarian cancer, lung cancer, pancreatic cancer, melanoma, etc. CD38 promotes tumor proliferation, migration, and invasion by regulating intracellular Ca²⁺ signaling and immune escape.
3) Other diseases: Type 2 diabetes mellitus (CD38 is involved in insulin secretion and glucose metabolism), asthma (CD38 upregulation in airway smooth muscle cells enhances inflammatory responses and airway hyperresponsiveness), age-related diseases (CD38 mediates NAD⁺ decline with aging), and autoimmune diseases.

Introduction of CD38 (ADPRC1) Chimeric Antigen Receptor (CAR)

CD38 (ADPRC1) CAR is a chimeric antigen receptor specifically targeting the CD38 (ADPRC1) antigen, which is engineered to express on the surface of immune cells (T cells, NK cells) through plasmid vectors, enabling the immune cells to specifically recognize and kill CD38-positive tumor cells. The core structure of CD38 (ADPRC1) CAR consists of four parts: extracellular antigen-binding domain (anti-CD38 scFv), hinge region, transmembrane domain, and intracellular signal domain. Different generations of CARs are distinguished by the number and type of intracellular signal domains, with distinct functional characteristics.

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