CD33 positive

While previous CD33-targeting antibody-drug conjugates (ADCs) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window...The development of GLK-33 addresses the limitations of previous ADCs, offering a wider therapeutic window, improved tolerability, and activity against drug-resistant leukemia cells. These findings encourage further exploration of GLK-33 in AML through clinical trials.

Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development.

dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.

P1, N=18, Recruiting, Uma Borate | Trial primary completion date: Jan 2024 --> Jan 2025

P=N/A, N=165, Recruiting, Pfizer | Not yet recruiting --> Recruiting

CD166 positive cells were relatively resistance to apoptosis. Together our results demonstrate the anticancer efficacy of Ag-Au NC mediated by a mechanism involving cell cycle arrest and mitochondrial derangement.

P1, N=26, Active, not recruiting, Medical College of Wisconsin

In conclusion, we have developed a novel immunotherapy approach using engineered NK cells, which are easy to produce and exhibit promising efficacy. Given these data, anti-CD33 CAR-IL-33-IL-15-modified NK cells are a candidate for further development toward clinical translation for the treatment of acute myelogenous leukemia (AML).

Two members of the G6Pase system, G6PC3 and SLC37A4, associate with GBM disease progression and regulate the metabolic reprogramming of an invasive and CSC phenotype. Such molecular signature may support their role in cancer cell survival and chemoresistance and become future therapeutic targets.

P1, N=27, Recruiting, City of Hope Medical Center | Trial completion date: Nov 2025 --> Sep 2026 | Trial primary completion date: Nov 2025 --> Sep 2026

The disease was refractory to induction therapy with daunorubicin and cytarabine (DNR/Ara-C) and to reinduction therapy with mitoxantrone, etoposide, and cytarabine (MEC). After two cycles of VEN/AZA, the pericardial and pleural effusion disappeared, and complete remission was achieved. The patient received post-transplant cyclophosphamide-based haploidentical transplantation and has stayed relapse-free as of her last follow-up examination 2 years after diagnosis.

P1, N=26, Active, not recruiting, Medical College of Wisconsin | Trial primary completion date: Oct 2024 --> May 2024

P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Gemtuzumab Ozogamicin (GO), a monoclonal antibody targeting CD33, linked to calicheamicin, is approved in combination with daunorubicin and cytarabine (3+7) for the treatment of patients with previously untreated, de novo CD33-positive non promyelocytic AML...Figura 1. Overall survival of the whole population (34 cases) from the diagnosis.

P2, N=50, Recruiting, Centre Antoine Lacassagne | Not yet recruiting --> Recruiting

We used a CAR-T cell consisting of a CD33 binder and CD28z-OX40 costimulatory moiety...2). Our work provides critical information to overcome resistance to CAR-T cell treatment by neutralising the negative effects of the stromal microenvironment.

However, targeting CD33 e.g. with the antibody-drug conjugate (ADC) gemtuzumab ozogamicin often leads to prolonged cytopenia due to suppression of normal myelopoiesis...Similar to HSPCs devoid of CD33 these engineered cells could enable tumor-selective immunotherapy using ADCs or CAR T cells but with preserved CD33 expression and function. Furthermore, since base editing is suitable for multiplexing, they may in the future be multiplexed to protect CD33 and other targets for combination immunotherapy.

During the first induction treatment, most patients (98.1%; n=105/107) received GO in association with other agents, most commonly cytarabine and daunorubicin (60.0%; n=63/105)... GO was predominantly administered according to its indication. Response rates were similar to those reported in the pivotal ALFA-0701 study. Median OS was longer in this study than in ALFA-0701 (49.8 vs 27.5 months), although median RFS and EFS were reduced.

The combination of lintuzumab-Ac225 and venetoclax had a manageable safety profile and no early mortality at day 30. The MTD was not reached and no significant toxicities have been reported during the follow-up period. Modified dosing schedule in Cohort 4 of the combination demonstrated improved anti-leukemic effects.

Building on the successes achieved by the recent trial from this consortium (NOPHO-DBH AML-2012, preliminary data as per June 2023, n=878: 5-years pEFS 63%, 5-years pOS 78%), CHIP-AML22 will incorporate innovative elements, mainly the FLT3-inhibitor quizartinib (Vanflyta®) that was recently approved by the FDA and PMDA in combination with chemotherapy for the treatment of newly diagnosed adult AML patients with FLT3-ITD mutations, and gemtuzumab ozogamicin (GO, Mylotarg®) that improved outcome in adult and pediatric AML when added to chemotherapy...Further, dexrazoxane is recommended to all patients before receiving daunorubicin or mitoxantrone, aiming to prevent late-onset cardiotoxicity...Study Ri and the linked quizartinib trial are expected to open in Q4 2023. At least 15 other countries with nearly 60 sites will participate in CHIP-AML22: Belgium, Denmark, Estonia, Finland, Hong Kong, Iceland, Israel, Latvia, Lithuania, Norway, Portugal, Spain, Sweden, Switzerland and Uruguay.

P2, N=26, Completed, New York Medical College | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

Up to 20% long-term gene editing in HSPCs and blood cell lineages was seen with robust loss of CD33 detection on myeloid lineages. In conclusion, deletion of the V-set domain of CD33 on HSPCs, progenitors, and myeloid lineages did not show any adverse effects on their homing and engraftment potential or the differentiation and functionality of myeloid progenitors and lineages.

This study reveals functional interaction and molecular mechanisms of m6A-modified circEPHB4 in regulating SOX2/PHLDB2 axis, highlighting their importance in glioma pathogenesis and potential as therapeutic targets.

Introduction: Gemtuzumab Ozogamicin (GO) in combination with 7+3 is approved in Germany for first-line-therapy of CD33-positive AML. Our retrospective analysis shows an increased rate of gastro-intestinal toxicity of patients treated with 7+3+ GO compared to 7+3 +/- Midostaurin. Although the results were not statistically significant due to a small number of patients available for the GO-cohort our findings suggest to carefully observe patients assigned for GO treatment especially if they are known to have pre-existing gastro-intestinal diseases.

CD33-M2T has demonstrated clear advantages over anti-CD33 monoclonal antibodies (e. g. , gemtuzumab, lintuzumab), including the ability to bind to the truncated alternatively spliced version of CD33, long duration of action, and no overt toxicities in mice. Conclusions These experiments demonstrate the preclinical potential of an innovative immunotherapy targeting CD33-positive childhood AML.

Myeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.

P1, N=102, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital

She was started on Remdesivir for COVID infection...Covid is more related to leukopenia, and most of the patients with LR associated with Filgrastim have been undergoing chemotherapy... LR as a first manifestation or further development during malignancies are rare. However, a proper workup must be performed to rule out leukemia and clarify if the LR is due to base malignancy or a secondary disease. AMS overall in patients with malignancies is ominous of poor prognosis

P1/2, N=38, Recruiting, Actinium Pharmaceuticals | Trial completion date: Jan 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Nov 2023

She was treated with CPX-351 (a liposomal formulation of cytarabine and daunorubicin) and venetoclax and repeat bone marrow biopsy no longer showed a complex karyotype...While there are no randomized controlled trials, treatment typically consists of chemotherapy and hematopoietic stem cell transplantation. Figure: Retroflexed view of myeloid sarcoma presenting as a gastric mass.

P1/2, N=0, Withdrawn, Actinium Pharmaceuticals | N=38 --> 0 | Not yet recruiting --> Withdrawn

BIRC5-206 might facilitate NPC tumor progression by inducing the transformation of NPC cells to cancer stem cells.

P=N/A, N=30, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P2, N=146, Not yet recruiting, Technische Universität Dresden

P1, N=27, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Initiation date: May 2023 --> Aug 2023

He was initially treated with VCD regimen (1.3 mg/ m2 bortezomib for days 1, 4, 8, and 11 , cyclophosphamide 50 mg oral daily, and dexamethasone 40 mg weekly) and Decitabine 20 mg/m2 ,5 days. Coclusions: The coexistence of MDS and MM is a very rare condition. Standard treatment methods are still absent, generally have low response rates to treatment and show a poor prognosis.

Eight patients received Fla-Ida (fludarabine, cytarabine, idarubicin), Fla-Ida-venetoclax or mini-Fla-Ida as part of an induction regimen. One patient required a salvage regimen with venetoclax -azacitidine prior to achieving complete remission... Our data identified genetic mutations in WT1 , NOTCH1 , RAS , FLT3 , RUNX1 , TP53, IKZF1, BCOR , ETV6 , IDH1/2 and U2AF1, with WT1 as the most common mutation in our cohort of T/M-MPAL patients. Fla-Ida is effective to bridge to alloHSCT. The outcome of patients without alloHSCT is very poor.

Also, we addressed predictors of response, being CD33 expression and SNPs, PgP-1 and Annexin A5. The near finalized intent-to-file clinical trial in the MyeChild consortium investigates whether fractionated dosing has additional value for pediatric AML, which may pave the way for a broader application of GO in pediatric AML.

Fractionated GO dosing regimen (3 mg/m/dose) is not predicted to pose a clinically significant safety risk for QT interval prolongation in patients with R/R AML. TEAEs are consistent with GO's known safety profile, and ADA presence appears unassociated with potential safety issues.

P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2022 --> Nov 2024 | Trial primary completion date: Nov 2022 --> Nov 2024

In this study, we demonstrate CD33 ARC alpha targeted radiotherapy depletes human CD33 positive immune suppressing MDSCs present in multiple cancer types, to enhance antitumor immunity. These findings present a translatable strategy that supports further evaluation of 225Ac lintuzumab as a MDSC targeting agent to improve the efficacy of antitumor therapies.