Xenetic Biosciences, Inc. Presents Positive Preclinical Data Highlighting the Potential of Co-Administration of DNase I with CAR T Cells in a Murine Model of Melanoma Lung Metastasis
Xenetic Biosciences (NASDAQ:XBIO) presented positive preclinical data showing the potential of co-administering DNase I with CAR T cells in treating melanoma lung metastasis. The study demonstrated that a single injection of DNase I (10 mg/kg) with EGFR-CAR T cells significantly suppressed metastatic tumor burden and extended survival compared to CAR T cell therapy alone. Key findings showed that DNase I increases tumor-infiltrating T and CAR T cells while reducing immunosuppressive effects. The research supports DNase I's potential as an adjunctive treatment to improve CAR T cell therapy responses, particularly in solid tumors where traditional CAR T cell therapy has shown efficacy.
Xenetic Biosciences (NASDAQ:XBIO) ha presentato dati preclinici positivi che mostrano il potenziale della co-somministrazione di DNase I con cellule CAR T nel trattamento delle metastasi polmonari del melanoma. Lo studio ha dimostrato che un'unica iniezione di DNase I (10 mg/kg) con cellule EGFR-CAR T ha significativamente ridotto il carico tumorale metastatico e ha prolungato la sopravvivenza rispetto alla terapia con cellule CAR T da sola. Risultati chiave hanno evidenziato che DNase I aumenta le cellule T infiltranti del tumore e le cellule CAR T, riducendo al contempo gli effetti immunosoppressivi. La ricerca supporta il potenziale di DNase I come trattamento adiuvante per migliorare le risposte della terapia con cellule CAR T, in particolare nei tumori solidi dove la terapia tradizionale con cellule CAR T ha dimostrato di avere efficacia.
Xenetic Biosciences (NASDAQ:XBIO) presentó datos preclínicos positivos que muestran el potencial de coadministrar DNase I con células CAR T en el tratamiento de las metástasis pulmonares de melanoma. El estudio demostró que una sola inyección de DNase I (10 mg/kg) con células EGFR-CAR T suprimió significativamente la carga tumoral metastásica y prolongó la supervivencia en comparación con la terapia solo con células CAR T. Hallazgos clave mostraron que DNase I incrementa las células T infiltrantes del tumor y las células CAR T, a la vez que reduce los efectos inmunosupresores. La investigación respalda el potencial de DNase I como un tratamiento adyuvante para mejorar las respuestas de la terapia con células CAR T, particularmente en tumores sólidos donde la terapia tradicional con células CAR T ha mostrado eficacia.
Xenetic Biosciences (NASDAQ:XBIO)는 멜라노마 폐 전이 치료를 위해 DNase I과 CAR T 세포를 병용 투여하는 잠재력을 보여주는 긍정적인 전임상 데이터를 발표했습니다. 이 연구는 EGFR-CAR T 세포와 함께 DNase I(10 mg/kg)의 단일 주사가 CAR T 세포 치료 단독에 비해 전이성 종양 부담을 유의미하게 억제하고 생존을 연장했음을 보여주었습니다. 핵심 발견은 DNase I이 종양 침투 T 세포와 CAR T 세포를 증가시키고 면역 억제 효과를 줄인다는 것을 보여주었습니다. 이 연구는 DNase I이 특히 전통적인 CAR T 세포 치료가 효과를 보였던 고형 종양에서 CAR T 세포 치료의 반응을 개선하는 보조 치료로서의 잠재력을 지지합니다.
Xenetic Biosciences (NASDAQ:XBIO) a présenté des données précliniques positives montrant le potentiel de co-administrer la DNase I avec des cellules CAR T dans le traitement des métastases pulmonaires du mélanome. L'étude a démontré qu'une seule injection de DNase I (10 mg/kg) avec des cellules EGFR-CAR T a significativement réduit la charge tumorale métastatique et prolongé la survie par rapport à la thérapie CAR T seule. Résultats clés ont montré que la DNase I augmente les cellules T infiltrantes tumorales et les cellules CAR T tout en réduisant les effets immunosuppresseurs. La recherche soutient le potentiel de la DNase I en tant que traitement adjuvant pour améliorer les réponses de la thérapie CAR T, en particulier dans les tumeurs solides où la thérapie traditionnelle CAR T a montré son efficacité.
Xenetic Biosciences (NASDAQ:XBIO) hat positive präklinische Daten präsentiert, die das Potenzial der gleichzeitigen Verabreichung von DNase I mit CAR T-Zellen bei der Behandlung von Melanom-Lungenmetastasen zeigen. Die Studie zeigte, dass eine einzelne Injektion von DNase I (10 mg/kg) mit EGFR-CAR T-Zellen die metastatische Tumorlast signifikant reduzierte und die Überlebenszeit im Vergleich zur alleinigen CAR T-Zelltherapie verlängerte. Wichtige Ergebnisse zeigten, dass DNase I die tumorinfiltrierenden T- und CAR T-Zellen erhöht und gleichzeitig immunosuppressive Effekte reduziert. Die Forschung unterstützt das Potenzial von DNase I als begleitende Therapie zur Verbesserung der Antworten auf die CAR T-Zelltherapie, insbesondere bei soliden Tumoren, bei denen die traditionelle CAR T-Zelltherapie Wirksamkeit gezeigt hat.
- Single DNase I injection with CAR T cells demonstrated significant suppression of metastatic tumor burden
- Treatment showed substantial survival prolongation compared to CAR T cell monotherapy
- DNase I increased tumor-infiltrating T and CAR T cells effectiveness
- Program advancing towards Phase 1 clinical development for pancreatic carcinoma and other solid tumors
- None.
Insights
The preclinical data demonstrates compelling efficacy for DNase I co-administration with CAR T cells in treating melanoma lung metastasis. Key findings include significant suppression of metastatic tumor burden, reduced metastatic foci and extended survival compared to CAR T monotherapy.
The mechanism of action is particularly noteworthy - DNase I degrades neutrophil extracellular traps (NETs) in the tumor microenvironment, which typically inhibit CAR T cell function. This leads to increased tumor infiltration by T cells and CAR T cells, while reducing immunosuppression. Importantly, the treated group showed lower expression of exhaustion markers (PD-1 and TIM-3) on CD8+ CAR T cells, suggesting improved T cell function and persistence.
For a micro-cap company (
Data presented at the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer
Results bolster Company's rationale for incorporating DNase I as an adjunctive treatment to improve therapeutic responses in patients undergoing CAR T cell therapy
FRAMINGHAM, MA / ACCESSWIRE / November 21, 2024 / Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard to treat cancers, today announced the presentation of preclinical data investigating the potential of co-administration of deoxyribonuclease I (DNase I) with chimeric antigen receptor (CAR) T cells in a syngeneic B16 melanoma murine model of lung metastasis.
The poster titled, "The synergistic action of DNase I and CAR T cells enhances the therapeutic efficacy of adoptive immunotherapy in the syngeneic murine metastasis model," was presented on behalf of the Company by Alexey Stepanov, PhD, Institute Investigator at The Scripps Research Institute, at the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer, held November 17-20, 2024, in Boston.
"Xenetic's proprietary DNase-based oncology platform continues to demonstrate encouraging potential across a number of cancer indications and therapy modalities where there remains significant unmet need. CAR T cell therapy is a promising approach for treating various malignancies however, it has so far shown benefit only in hematological cancers, so efficacy in solid tumors remains an important goal. There, its antitumor activity is often hindered by a hostile, immunosuppressive tumor microenvironment (TME), which, in turn, is very often characterized by the presence of tumor-associated cell-free DNA (cfDNA) in the form of neutrophil extracellular traps (NETs). This research underscores the critical role of the NETs in modulating CAR T cell efficacy and the potential of DNase I to improve therapeutic responses for patients as an adjunctive treatment. Highlighted by the results seen with the co-administration of DNase I with murine EGFR-CAR T cells, we believe this approach has the potential to prolong survival compared to treatment with CAR T cell monotherapy," commented Reid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic. "We continue to be encouraged by the data demonstrated to date and look forward to further exploring the translational potential of this combinatorial approach in enhancing cancer treatment."
For the preclinical study co-administration of DNase I with CAR T cells was investigated in a syngeneic B16 murine melanoma model of lung metastasis. Bioluminescent imaging of melanoma metastatic processes has shown that a single injection of DNase I (10 mg/kg) together with CAR T cells suppressed B16-EGFR lung metastasis at early stages in comparison to the vehicle control group and extended survival.
Key Highlights
Co-administration of single injection of DNase I (10 mg/kg) with murine EGFR-CAR T cells demonstrated to significantly suppress metastatic tumor burden, decreases the number of metastatic foci, and substantially prolongs survival compared to the CAR T cell monotherapy group.
Degrading of NETs by DNase I increases the amount of tumor-infiltrating T and CAR T cells and reduces the immunosuppressive effects of the TME.
Tumor immune cell infiltrate analysis revealed that the CD8 population of tumor-infiltrating CAR T cells from the DNase I treated group have lower expression of PD-1 and TIM-3 exhaustion markers.
Xenetic continues to advance its DNase-based oncology program towards Phase 1 clinical development for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors. Preliminary preclinical studies evaluating the combinations of DNase I with chemotherapy and DNase I with immuno-therapies in colorectal cancer models as well as CAR-T therapy have been completed.
About Xenetic Biosciences
Xenetic Biosciences, Inc. is a biopharmaceutical company focused on advancing innovative immune-oncology technologies addressing hard to treat cancers. The Company's DNase platform is designed to improve outcomes of existing treatments, including immunotherapies, by targeting neutrophil extracellular traps (NETs), which are involved in cancer progression. Xenetic is currently focused on advancing its systemic DNase program into the clinic as an adjunctive therapy for pancreatic carcinoma and other locally advanced or metastatic solid tumors.
For more information, please visit the Company's website at www.xeneticbio.com and connect on Twitter, LinkedIn, and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements that we intend to be subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release other than statements of historical facts may constitute forward-looking statements within the meaning of the federal securities laws. These statements can be identified by words such as "expects," "plans," "projects," "will," "may," "anticipates," "believes," "should," "intends," "estimates," "remain," "focus", "confidence in", "potential", and other words of similar meaning, including, but not limited to, all statements regarding expectations for our DNase-based oncology platform, including statements regarding: the potential of co-administration of deoxyribonuclease I (DNase I) with chimeric antigen receptor (CAR) T cells in a syngeneic B16 melanoma murine model of lung metastasis; the DNase-based oncology platform continuing to demonstrate encouraging potential across a number of cancer indications and therapy modalities where there remains significant unmet need; efficacy of CAR T cell therapy in solid tumors remaining an important goal; our belief that this approach has the potential to prolong survival compared to treatment with CAR T cell monotherapy; continuing to be encouraged by the data demonstrated to date and looking forward to further exploring the translational potential of this combinatorial approach in enhancing cancer treatment; our focus on advancing innovative immune-oncology technologies addressing hard to treat cancers; the DNase platform improving outcomes of existing treatments, including immunotherapies, by targeting neutrophil extracellular traps (NETs), which are involved in cancer progression; and our focus on advancing our systemic DNase program towards Phase 1 clinical development as an adjunctive therapy for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors. Any forward-looking statements contained herein are based on current expectations and are subject to a number of risks and uncertainties. Many factors could cause our actual activities, performance, achievements, or results to differ materially from the activities and results anticipated in forward-looking statements. Important factors that could cause actual activities, performance, achievements, or results to differ materially from such plans, estimates or expectations include, among others, (1) unexpected costs, charges or expenses resulting from our manufacturing and collaboration agreements; (2) unexpected costs, charges or expenses resulting from the licensing of the DNase platform; (3) uncertainty of the expected financial performance of the Company following the licensing of the DNase platform; (4) failure to realize the anticipated potential of the DNase or PolyXen technologies; (5) the ability of the Company to obtain funding and implement its business strategy; and (6) other risk factors as detailed from time to time in the Company's reports filed with the SEC, including its annual report on Form 10-K, periodic quarterly reports on Form 10-Q, current reports on Form 8-K and other documents filed with the SEC. The foregoing list of important factors is not exclusive. In addition, forward-looking statements may also be adversely affected by general market factors, general economic and business conditions, including potential adverse effects of public health issues, such as the COVID-19 outbreak, and geopolitical events, such as the conflicts in the Ukraine and in the Middle East, on economic activity, competitive product development, product availability, federal and state regulations and legislation, the regulatory process for new product candidates and indications, manufacturing issues that may arise, patent positions, litigation, and shareholder activism, among other factors. The forward-looking statements contained in this press release speak only as of the date the statements were made, and the Company does not undertake any obligation to update forward-looking statements, except as required by law.
Contact:
JTC Team, LLC
Jenene Thomas
(908) 824-0775
xbio@jtcir.com
SOURCE: Xenetic Biosciences, Inc.
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FAQ
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