Marker Therapeutics Reports MT-401 Non-Clinical Data in AML Cells after Hypomethylating Agent Administration
The multiTAA-specific T cell technology from Marker uses a novel non-genetically modified T cell therapy approach that recognizes multiple antigens expressed on tumor cells, thereby designed to minimize tumor escape. MT-401 was designed to specifically target four different antigens (Survivin, PRAME, WT-1 and NY-ESO-1), which are upregulated in AML but have limited expression on normal cells.
In
One such opportunity is to combine multiTAA-specific T cell therapy with agents that make cancer cells more visible to cancer killing cells. This opportunity has practical merit because HMAs that do this, such as 5’-Azacytidine and Decitabine, are commonly used as therapies for AML. It also has scientific merit because these agents inhibit DNA methylation, a process which regulates gene expression. By reducing DNA methylation, HMAs can restore physiological gene expression patterns, including the upregulation of tumor suppressor genes, and the inhibition of oncogenes. HMAs have also been found to upregulate the expression of tumor antigens, including MT-401-specific tumor antigens, previously silenced by DNA methylation (Wong et al, Front Oncol, 2021).
Due to this mechanism of action,
- In this in vitro model of treatment resistant AML, tumor cells exposed to HMA for 72 hours upregulated tumor-associated antigen targets of MT-401, including Survivin.
- The THP-1 cell line was bioluminescent modified to allow real-time long-term assessment of cancer cell growth.
- THP-1 cells continued to grow both in the absence and presence of DMSO, the vehicle used to dissolve 5’-Azacytidine.
- The growth of THP-1 cells was reduced in the presence of 5’-Azacytidine (after exposure to the drug for 72 hours).
- The growth of THP-1 cells was also reduced in the presence of MT-401 (manufactured from donors that were partially HLA-matched to THP-1 cells).
- THP-1 cell growth, however, was significantly decreased when MT-401 was added after exposure to 5’-Azacytidine compared to MT-401 or 5’-Azacytidine administration alone, suggesting a synergistic effect between the two agents.
- These in vitro data demonstrate that administration of MT-401 following HMA infusion enhanced AML cell killing and could offer a new therapeutic option for AML patients post-HSCT.
“These non-clinical findings highlight that the potential for treatment of AML cells with HMA to upregulate expression of specific tumor antigens and increase tumor inhibition and killing. These benefits could therefore significantly enhance the potential clinical outcome of our multiTAA-specific T cell product,” said
Based on this non-clinical data, Marker received a
“We are pleased to receive the SBIR grant from the
“We previously observed promising results in our Phase 2 ARTEMIS trial for patients with AML who are MRD+ post-transplant, suggesting that MT-401 can effectively positively impact this patient population before relapse. The SBIR grant will greatly contribute to further advance our clinical trial and to investigate the benefit of HMA administration before MT-401 therapy in patients after HSCT, and for whom no treatments have been approved,” concluded
About the NIH SBIR Program
About multiTAA-specific T cells
The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient's/donor’s blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 180 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated, demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect. Unlike other cell therapies which require hospitalization and close monitoring, multiTAA-specific T cells are designed to be administered in an outpatient setting.
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Forward-Looking Statements
This release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this news release concerning the Company’s expectations, plans, business outlook or future performance, and any other statements concerning assumptions made or expectations as to any future events, conditions, performance or other matters, are “forward-looking statements.” Forward-looking statements include statements regarding the Company’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the Company’s research, development and regulatory activities and expectations relating to the Company’s non-engineered multi-tumor antigen specific T cell therapies; the effectiveness of these programs or the possible range of application and potential curative effects and safety in the treatment of diseases; and the timing, conduct and success of the Company’s clinical trials of our its product candidates, including MT-401 for the treatment of patients with AML. Forward-looking statements are by their nature subject to risks, uncertainties and other factors which could cause actual results to differ materially from those stated in such statements. Such risks, uncertainties and factors include, but are not limited to the risks set forth in the Company’s most recent Form 10-K, 10-Q and other SEC filings which are available through EDGAR at WWW.SEC.GOV. The Company assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
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Source: Marker Therapeutics