CD38 expression

In the preclinical setting, MT-0169 effectively lysed primary MM cells from newly diagnosed and heavily pretreated MM patients, including those refractory to daratumumab, with minimal toxicity against nonmalignant hematopoietic cells. Finally, MT-0169 showed efficient in vivo anti-MM activity in various mouse xenograft models, including one in which MM cells are grown in a humanized bone marrow-like niche. These findings support clinical investigation of MT-0169 in relapsed/refractory MM patients, including those refractory to CD38-targeting immunotherapies.

Tal-DP exhibits a deep, long-term impact on efficacy through complementary mechanisms of action and may be especially beneficial in pts with prior BsAb exposure, who typically have unfavorable BL immune profiles. Ongoing analyses of tec-DP from MajesTEC-2 (NCT04722146) will be presented.

Together, this highlights CD38 as an important regulator of CD45 activity via CD43 and galectin-1, in turn acting as a positive modulator of CLL proliferation. Ultimately, the CD38/CD45 molecular hub could be an important therapeutic target in CLL.

The aim of this study was to evaluate, using multi-colour flow cytometry, the level of CLL-1 protein expression on CD34+CD38- myeloid niche cells in acute myeloid leukaemia (AML) and myelodysplastic syndromepatients at the time of diagnosis and during disease monitoring on the example of 3 practical cases. The following conclusion was drawn: CD34+CD38-CLL-1+ cells in AML patients may serve as a biomarker to predict disease aggressiveness.

P1, N=9, Completed, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Completed

However, plasma cells were largely unchanged, and NK-cells expressing CD38 - the daratumumab target antigen - increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.

Finally, the present study suggested the log Firmicutes/Bacteroidota ratio as a novel intestinal microbiome signature associated with a shorter time to first treatment in individuals with CLL. The findings indicate that oral and gut microbial diversity in CLL might point to the inflammatory-related modulation of the clinical course of the disease.

Specifically, absolute counts of NK cells ≤72.0 cells/μl, CD4(+)CD28(+)/CD4(+) T >94.2%, and CD8(+)CD28(+)/CD8(+) T >38.4% were identified as risk factors for predicting the development of NHL-HLH patients. This will assist in early clinical diagnosis and treatment.

Our data demonstrate the association between CD146 expression and Ph+ ALLs. CD146, along with myeloid markers, may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in the diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.

The MCs in AML-MC cases are characterized by dim CD45, low side scatter, CD34 and CD123 positivity, and uniform and increased CD38 expression. Flow cytometry is an excellent tool for identifying AML-MC cases.

Our preliminary data suggest that the immune-related markers signature in the healthy peritumoral mucosa might be useful for predicting relapse after adjuvant therapy in rectal cancer patients. Moreover, relapsing patients showed lower stimulation of macrophages and lymphocytes, thus suggesting that impaired immune surveillance might influence adjuvant therapy outcomes. Sampling healthy mucosa might help the decision-making about adjuvant therapy after surgery for rectal cancer.

Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

In vivo data confirmed that tinostamustine pretreatment followed by daratumumab administration significantly delayed tumor growth and improved the survival of mice compared to individual treatments. In summary, our results suggest that tinostamustine could be a potential candidate to improve the efficacy of anti-CD38 mAbs.

Potent DHODHi to date have been limited by their therapeutic index; however, we introduce pharmacodynamic monitoring to predict tolerability while preserving antitumor activity. We additionally suggest that DHODHi is effective at lower doses with select immune therapies, widening the therapeutic index.

ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

Furthermore, based on the effect of ARG2 on the malignant phenotype of PCa in vitro, we also found that ARG2 may be a tumor suppressor that plays an important role in inhibiting proliferation, migration, and invasion. These findings suggest that ARG2 has been tentatively identified as a new target for research into how PCa develops in metabolism and for the development of innovative targeted treatments.

A combination of cisplatin/etoposide, ICB, and CD38 blockade delayed tumor growth compared to cisplatin/etoposide. Our study provides a preliminary but important direction toward exploring CD38 as a potential biomarker of ICB response and CD38 blockade as a combination strategy for chemo-immunotherapy in SCLC.

The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

P1, N=61, Active, not recruiting, Hangzhou Sumgen Biotech Co., Ltd. | Withdrawn --> Active, not recruiting | Trial completion date: Oct 2022 --> Dec 2024 | Trial primary completion date: Sep 2022 --> Jun 2024

P=N/A, N=1248, Completed, Northwell Health | Active, not recruiting --> Completed | Trial completion date: Feb 2025 --> Sep 2023 | Trial primary completion date: Jan 2025 --> Sep 2023

Daratumumab (dara), a monoclonal antibody (mAb) that targets CD38 results in antibody-dependent cellular cytotoxicity (ADCC) of both multiple myeloma (MM) cells and NK cells. Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity in vitro.

Knockdown of RyR2 or inhibition of AKT in CD8+ T cells maintained TCF1 levels, induced a sustained anti-tumor response, and enhanced responsiveness to anti-PD1 therapy. Thus, targeting CD38 represents a potential strategy to improve the efficacy of anti-PD1 treatment in cancer.

P2, N=50, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Nov 2023

In conclusion, [68 Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68 Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.

P2, N=50, Not yet recruiting, PETHEMA Foundation

Critically, while BN-CD38 showed significant in vivo efficacy across multiple disseminated AML cell lines and patient derived xenograft models, it did not affect normal hematopoietic stem cell clonogenicity and the development of multi-lineage human immune cells in CD34pos humanized mice. Taken together, this study provides important insights to target and eliminate AML LSCs.

Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.

P1, N=102, Terminated, Sanofi-Aventis Australia Pty Ltd | Active, not recruiting --> Terminated

The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Further, we provide evidence that, unlike anti-CD38 CAR-T, which elicited a rapid immune reaction against hematopoietic cells in a humanized mouse model, DCAR-T showed no signs of toxicity. Thus, DCAR-T could provide a safe and efficient alternative to anti-BCMA CAR-T to treat MM patients.

P1, N=15, Recruiting, City of Hope Medical Center | Suspended --> Recruiting

Patients with poor cytogenetic risk were associated with significantly shorter median overall survival when compared to favorable and intermediate cytogenetic risk (p =0.010). The expression of CD38 significantly adds to the prognostic value of cytogenetic risk stratification at diagnosis of AML patients.

P1, N=11, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Dec 2025 --> Jan 2024

P1, N=15, Suspended, City of Hope Medical Center | Recruiting --> Suspended

This study indicated biological significance of rs1130169 variations that can alter differences in CRC risk by regulating CD38 gene expression.

P=N/A, N=53, Completed, Boston Medical Center | Active, not recruiting --> Completed

CD38 knock-out CAR NK cells also demonstrated significantly higher levels of NK activation markers in co-cultures with both untreated and αCD38-treated MM cell lines. These NAM-cultured NK cells with the combined genetic approach of CD38 knockout and addition of CD38 CAR represent a promising immunotherapeutic tool to target MM.

The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.

Peptide probes were labeled with indocyanine green (ICG) dye and Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

This study aimed to determine whether selinexor augments NK cell activation against MM cells both alone, and in combination with the anti-CD38 antibody daratumumab. These data suggest that selinexor may promote the efficacy of NK targeted therapeutics in multiple myeloma.

It is interesting to uncover novel pathways for drug discovery and clinic treatment since CD38 is well expressed in most AML patients, but at least half of those CD38 + AML patients are not sensitive or resistant to Daratumumab monotherapy...PD1 antibody Sintilimab has been tested in all the patients (12 lymphoma, 52 leukemia), and the only two laboratory PD1-Ab non-responsive T cell lymphoma patients have been showed to be clinically non-responders as well. Immunotherapy and chemical or targeted therapy combination could enhance tumor killing ability and disease control. We will use the IO-FIVE data to further compare it with its source of real-world clinical patients to obtain more evidence-based evidence that can predict individualized treatment with immunotherapy.

Based on these observations, we conclude that CD123 density, blast cells and T-cell subsets in WB and BM samples from AML patients were stable for 48 h in our experimental conditions. As a consequence, fresh WB and BM samples can be processed and analyzed by qFC within 48 h of sample collection. Furthermore, the new cryopreservation method showed sample stabilization for blasts and T cells immunophenotyping.