Overview of CD138-Targeted CAR Cell Therapies

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Creative Biolabs, a CRO solution provider, was established and is managed by a group of seasoned scientists and experts with a wealth of expertise and experience in cell therapy R&D. We are committed to offering the finest products and services in the academic and industrial domains around the world, helping to drive forward preclinical and clinical research for innovative scientific breakthroughs.

Background of CD138

CD138, also known as Syndecan-1, is a transmembrane protein widely present on the surface of mammalian cells. It has a gene size of around 27.5 kilobase pairs (kbp) and comprises of six exons and five introns. The gene is expressed in various cell types, including tumor cells and hematopoietic stem cells. The primary function of CD138 is to act as a binding receptor for collagen fibrils and other extracellular matrix molecules, participating in biological processes such as cell adhesion, migration, and signal transduction. CD138 is also involved in B-cell differentiation and antibody production, as well as in the regulation of plasma cell survival and migration. Besides its role in plasma cells, CD138 is expressed on the surface of several other cell types, including epithelial cells, fibroblasts, and certain types of cancer cells. Expression of CD138 on epithelial cells is thought to play a critical role in wound healing and tissue repair, as well as in the regulation of inflammation. And CD138 is highly expressed in several malignancies, especially in multiple myeloma (MM), where it is widely used as a diagnostic and therapeutic target.

Fig.1 Structure of CD138

CD138 Signaling Pathways

CD138 regulates several signaling pathways and plays a crucial role in physiological and pathological processes. For example, CD138 can regulate NF-κB activity, thereby affecting biological processes such as immune response, apoptosis, and survival.

CD138 interacts with several receptor tyrosine kinases (RTKs) and activates them, thereby triggering the activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. For instance, in hepatocellular carcinoma cells, CD138 binds and autophosphorylates ectodermal growth factor (EGFR), which sebsequently activates the PI3K/Akt pathway, promoting cell proliferation and invasion.

CD138 activate the PI3K signaling pathway by directly binding to its subunit p85α. In breast and lung cancer cells, CD138 interacts directly with p85α through its C-terminal nonstructural domain region, promoting the activation of the PI3K/Akt pathway.

CD138 is also known to play a key role in melanoma proliferation, invasion and metastasis. It can form signal transduction complexes with other proteins, affecting the PI3K signaling pathway. For example, in melanoma, CD138 binds HER2 to form a complex with the PI3K subunit p85α, enhancing the activation of the PI3K/Akt pathway.

Clinic Status of CD138-Targeted CAR Cell Therapies

Chimeric Antigen Receptor (CAR)-T cells are a type of immune cell therapy in which the T cell receptor (TCR) on the surface of T cells is genetically modified into a chimeric antigen receptor that recognizes a specific antigen. When CAR-T cells encounter a specific antigen, they rapidly kill the tumor cells carrying that antigen. Thus, CD138 CAR-T cells are a specific type of CAR-T cell designed to target CD138-positive malignancies. CD138 CAR-T cell therapy has entered clinical trials, which include Phase I, II, and III clinical trials. Preclinical studies have demonstrated the effectiveness of CD138 CAR-T cell therapy in vivo and in vitro. These studies have shown that CD138 CAR-T cells can eliminate CD138-positive tumor cells in a multiple myeloma xenograft model, leading to tumor regression and prolonged survival. In addition, CD138 CAR-T cells have been shown to have specific cytotoxicity against CD138-positive ovarian and breast cancer cells.

In clinical trials, CD138 CAR-T cell therapies are still in the early stages of development. An ongoing Phase I clinical trial is evaluating the safety and efficacy of CD138 CAR-T cells in patients with relapsed or refractory multiple myeloma. The trial includes the infusion of CD138 CAR-T cells to patients to assess the safety and tolerability of the treatment and its potential efficacy in inducing disease remission.

A major challenge is identifying patients with CD138-positive tumors, as CD138 expression levels may vary between cancer types and different tumor subtypes. To address these challenges, future research directions for CD138 CAR-T cell therapy are focused on the following areas:

(1) Improving therapeutic efficacy: further optimizing CAR structures and signaling regions to improve the attack efficiency and survival of CAR-T cells and increase their killing effect on tumor cells.

(2) Reducing side effects: studying how to minimize side effects during CD138 CAR-T cell therapy and reduce the damage to normal tissues.

(3) Expanding the scope of indications: exploring the feasibility of CD138 CAR-T cells for the treatment of other CD138-positive tumors and conducting corresponding clinical trials.

(4) Developing combination therapy protocols.

Table 1. Ongoing CD138-Targeted CAR Cell Therapy Clinical Trials

NCT Number	Title	Status	Study Results	Conditions	Sponsor/Collaborators	Phases
NCT03672318	Study of ATLCAR.CD138 Cells for Relapsed/Refractory Multiple Myeloma	Recruiting	No Results Available	Multiple Myeloma\|Immune System Diseases	UNC Lineberger Comprehensive Cancer Center	Phase 1
NCT03196414	Study of T Cells Targeting CD138/BCMA/CD19/More Antigens (CART-138/BCMA/19/More) for Chemotherapy Refractory and Relapsed Multiple Myeloma	Recruiting	No Results Available	Multiple Myeloma	The First Affiliated Hospital of Soochow University	Phase 1\|Phase 2

References

Tang, Xiaowen, et al. "First-in-man clinical trial of CAR NK-92 cells: safety test of CD138-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia." American journal of cancer research 8.6 (2018): 1083.
Omstead, David T., et al. "In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma." Journal of Hematology & Oncology 13.1 (2020): 1-15.
Shuai, Wen, and Shaoying Li. "CD138− plasma cell myeloma." Blood, The Journal of the American Society of Hematology 134.11 (2019): 906-906.
McCarron, Mark J., Pyong Woo Park, and David R. Fooksman. "CD138 mediates selection of mature plasma cells by regulating their survival." Blood, The Journal of the American Society of Hematology 129.20 (2017): 2749-2759.
Mykytiv, Vitaliy, Abrar Alwaheed, and Nurul Asyikin Mohd Hashim. "Double CD38−/CD138− negative multiple myeloma." Hematology/oncology and stem cell therapy 12.1 (2019): 64-66.
Choudhuri, Jui, et al. "Cardiovascular Involvement of a CD138-Negative Anaplastic Myeloma: A Diagnostic Dilemma." Hematology Reports 15.1 (2023): 66-72.
Lin, Quande, et al. "Recent updates on CAR-T clinical trials for multiple myeloma." Molecular cancer 18.1 (2019): 1-11.