CD138, also known as syndecan-1, is an integral membrane protein widely expressed in differentiated plasma cells. Functioning as a receptor for the extracellular matrix through its extracellular domain, CD138 plays important roles in mediating multiple myeloma (MM) development and proliferation. These biological functions, in alliance with CD138’s high expression in MM cells, potentiate it a valuable immunotherapeutic target as well as a primary diagnostic marker for MM.
Anti-CD138 CAR-T/NK Cell Therapy
The vital role of CD138 in regulating multiple myeloma development promotes the enrolling of CD138-related clinical trials, such as CAR-T-138 (NCT01886976). In addition, anti-CD138 CAR modified NK cells have also shown therapeutic potential in CD138-positive plasmacytic malignancies in vivo. NK-92 cell line is the first one to be tested in several clinical trials with promising safety evaluation for clinical application (limited engraftment capacity and minimal organ toxicity). Nevertheless, modified NK-92 derivative NK-92MI cells that express anti-CD138 CAR fused to intrinsic signaling molecule revealed upgrading intrinsic cytotoxic potential of the effector cells and elevated capacity to extravagate and home to tumor sites. This renders the feasibility of further improving remission quality and prolonging the remission duration of patients with multiple myeloma after upfront chemotherapy.
Xenograft models for subcutaneously transplanted multiple myeloid are established by injection of CD138-positive cells (RPMI8226, U266 or NCI-H929) into the right flank of NOD/SCID mice. Intervention of modified T cells or NK cells via intravenously injection initiates when palpable tumors develops (≥5 mm in diameter). Tumor volume is measured and recorded regularly, and other endpoints are adopted according to specific demands.
Xenograft models for disseminated multiple myeloid are established by intravenously inoculating of luciferase-labeled CD138-positive cells (RPMI8226, U266 or NCI-H929) into NSG mice, and subsequently monitored through bioluminescent imaging. Intervention with modified T cells or NK cells initiates when the mean total flux of the tumor reaches between 107 and 108 photons/sec, via tail vein injection.
Patient-derived xenograft (PDX) models for multiple myeloid are also available at Creative Biolabs. The PDX models are developed with dissociated tumor cells from bone marrow biopsies of MM patients that can better reflect the heterogeneity and sophistication of tumors, which will benefit the evaluation of CAR-T/NK cell efficacy.
In vivo Assay Parameters and Techniques
At Creative Biolabs, we offer the most exquisite and comprehensive service platform for preclinical anti-CD138 CAR-T/NK cell therapy research.
Combinatorial or trans-signaling CAR strategies
Tumor remission monitored by bioluminescence imaging (BLI)
Survival curve tracking
Viability and Bio-distribution Studies
Tumor infiltration, CAR-T cell durability, GLP-compliant bio-distribution studies
Cytokine release analysis
Pilot tolerability (MTD, the route of administration, dose regimen / response / onset)
Clinical observation (body weight, behavior, feed consumption)
Complete necropsy/organ weight
GLP-Compliant Preclinical Test
All our experiments are performed by well-trained and experienced technicians in a GLP-compliant and IACUC-regulated facility.
Creative Biolabs has partnered with scores of research institutes and hospitals to get access to the resources such as patient primary samples, which are essential for the establishment of PDX models. The traditional xenograft models, in alliance with our PDX models, will better optimize the preclinical studies and further convert preclinical anti-CD138 CAR-T/NK therapy to a clinical benefit.
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