Xenetic Biosciences, Inc. Presents Positive Data Demonstrating DNase I Significantly Improves Efficacy of Anti-CTLA-4 Immune Checkpoint Blockade in Preclinical Colorectal Carcinoma Models
Xenetic Biosciences (NASDAQ:XBIO) presented positive preclinical data demonstrating that DNase I significantly enhances the effectiveness of anti-CTLA-4 immune checkpoint blockade in colorectal carcinoma models. The study showed that systemic DNase I combined with α-CTLA-4 antibody successfully promoted antitumor immunity and generated immunological memory against microsatellite stable, mismatch repair proficient colorectal carcinoma tumors. Key findings include tumor growth inhibition, complete responses in mice, and enhanced survival rates. The data suggests DNase I impedes neutrophil tumor infiltration while promoting T cell infiltration and activation, potentially addressing unmet needs in cancer treatments where immune checkpoint inhibitors have shown efficacy.
Xenetic Biosciences (NASDAQ:XBIO) ha presentato dati preclinici positivi che dimostrano come DNase I migliori significativamente l'efficacia del blocco del checkpoint immunitario anti-CTLA-4 nei modelli di carcinoma colorettale. Lo studio ha rivelato che DNase I sistemico combinato con anticorpo α-CTLA-4 ha promosso con successo l'immunità antitumorale e generato memoria immunologica contro tumori colorettali stabili microsatellite e proficienti nella riparazione degli errori. I principali risultati includono l'inibizione della crescita tumorale, risposte complete nei topi e tassi di sopravvivenza aumentati. I dati suggeriscono che DNase I ostacola l'infiltrazione tumorale dei neutrofili, promuovendo al contempo l'infiltrazione e l'attivazione delle cellule T, affrontando potenzialmente bisogni insoddisfatti nei trattamenti oncologici dove gli inibitori del checkpoint immunitario hanno dimostrato di essere efficaci.
Xenetic Biosciences (NASDAQ:XBIO) presentó datos preclínicos positivos que demuestran que DNase I mejora significativamente la efectividad del bloqueo de checkpoint inmunitario anti-CTLA-4 en modelos de carcinoma colorrectal. El estudio mostró que DNase I sistémico combinado con el anticuerpo α-CTLA-4 promovió exitosamente la inmunidad antitumoral y generó memoria inmunológica contra tumores colorrectales estables de microsatélites y proficientes en reparación de emparejamientos. Los hallazgos clave incluyen la inhibición del crecimiento tumoral, respuestas completas en ratones y tasas de supervivencia mejoradas. Los datos sugieren que DNase I impide la infiltración tumoral de neutrófilos mientras promueve la infiltración y activación de células T, lo que potencialmente aborda necesidades no satisfechas en tratamientos contra el cáncer donde los inhibidores de checkpoint inmunitario han demostrado eficacia.
제네틱 바이오사이언스 (NASDAQ:XBIO)는 DNase I가 대장암 모델에서 항 CTLA-4 면역 체크포인트 차단제의 효과를 상당히 향상시킨다는 긍정적인 전임상 데이터를 발표했습니다. 연구 결과 시스템 DNase I과 α-CTLA-4 항체의 조합이 항종양 면역을 성공적으로 촉진하고 마이크로위불렛 안정적이고 교정 복구가 능숙한 대장암 종양에 대한 면역 기억을 생성했음을 보여주었습니다. 주요 발견에는 종양 성장 억제, 생쥐에서의 완전한 반응, 그리고 향상된 생존률이 포함됩니다. 데이터는 DNase I이 호중구의 종양 침투를 방해하는 동시에 T 세포의 침투 및 활성화를 촉진하여 면역 체크포인트 억제제가 효과를 보여준 암 치료의 미충족 요구를 해결할 가능성을 제시합니다.
Xenetic Biosciences (NASDAQ:XBIO) a présenté des données précliniques positives montrant que DNase I améliore significativement l'efficacité du blocage du point de contrôle immunitaire anti-CTLA-4 dans des modèles de carcinome colorectal. L'étude a démontré que la DNase I systémique associée à l'anticorps α-CTLA-4 a réussi à promouvoir l'immunité antitumorale et à générer une mémoire immunologique contre des tumeurs colorectales stables en microsatellites et compétentes en réparation des mésappariements. Les principales conclusions comprennent l'inhibition de la croissance tumorale, des réponses complètes chez les souris et des taux de survie améliorés. Les données suggèrent que DNase I freine l'infiltration tumorale des neutrophiles tout en promouvant l'infiltration et l'activation des cellules T, ce qui pourrait répondre à des besoins non satisfaits dans les traitements du cancer où les inhibiteurs de point de contrôle immunitaire ont démontré leur efficacité.
Xenetic Biosciences (NASDAQ:XBIO) hat positive präklinische Daten vorgestellt, die zeigen, dass DNase I die Wirksamkeit der Anti-CTLA-4-Immuncheckpoint-Blockade in Modellen von kolorektalem Karzinom erheblich verbessert. Die Studie zeigte, dass systemisches DNase I in Kombination mit α-CTLA-4-Antikörpern erfolgreich die antitumorale Immunität förderte und immunologisches Gedächtnis gegen Mikrosatelliten-stabile, mismatch-repair-proficiente kolorektale Karzinome erzeugte. Zu den wichtigsten Ergebnissen gehören die Hemmung des Tumorwachstums, vollständige Antworten bei Mäusen und verbesserte Überlebensraten. Die Daten deuten darauf hin, dass DNase I die Tumorinfiltration von Neutrophilen hemmt, während es die Infiltration und Aktivierung von T-Zellen fördert, was potenziell unbefriedigte Bedürfnisse in der Krebsbehandlung anspricht, in denen Immuncheckpoint-Hemmer Wirksamkeit gezeigt haben.
- Successful preclinical results showing DNase I improves efficacy of immunotherapy
- Complete responses achieved in multiple mouse tumor models
- Evidence of lasting immunological memory in treated subjects
- Demonstration of tumor growth inhibition and enhanced survival
- Still in preclinical stage, requiring further development before clinical trials
- Results to animal models, human efficacy yet to be demonstrated
Insights
The preclinical data for Xenetic's DNase platform shows promising potential in enhancing immunotherapy effectiveness for colorectal cancer (CRC). The combination of DNase I with anti-CTLA-4 therapy demonstrated several complete responses and improved survival in mouse models, particularly noteworthy for microsatellite stable CRC where current immunotherapies typically fail.
Most significant is the development of immunological memory, evidenced by zero tumor growth upon rechallenge. This suggests potential for long-term therapeutic benefits. The mechanism targeting Neutrophil Extracellular Traps (NETs) addresses a key immunosuppressive barrier in the tumor microenvironment, potentially opening new treatment avenues for previously resistant cancers.
However, investors should note these are early-stage preclinical results. The path to clinical trials and eventual commercialization remains long and uncertain, typical for early-stage biotech developments. The small market cap of
Data presented at Society for Immunotherapy of Cancer (SITC) 2024
Systemic DNase I combined with 𝛼-CTLA-4 antibody demonstrated to promote antitumor immunity and generate immunological memory against microsatellite stable, mismatch repair proficient colorectal carcinoma (CRC) tumors
FRAMINGHAM, MA / ACCESSWIRE / November 12, 2024 / Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat oncology indications, today announced the presentation of positive preclinical data.
The poster titled, " DNase I Targeting of Neutrophil Extracellular Traps Improves CTLA-4 Immune Checkpoint blockade in Models of MSS/MMRp CRC ," was presented byReid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic at the Society for Immunotherapy of Cancer (SITC) 39 th Annual Meeting held on November 6-10, 2024, in Houston, Texas and virtually.
"We continue to be encouraged by the data demonstrated by our DNase platform technology. Several human cancers, including gastrointestinal cancers like colorectal cancers (CRC) in particular, have high levels of neutrophil infiltration and neutrophil extracellular traps (NETs), which contribute to an immunosuppressive, protumor microenvironment (TME), leading to poor response to therapies. Based on the growing body of data, we believe our DNase-based oncology platform has the potential to address the significant unmet need across a number of cancer indications where immune checkpoint inhibitors have not shown significant clinical utility to date, such as microsatellite stable, mismatch repair proficient (MSS/MMRp) CRC, which is the largest subset of CRC and where immune checkpoint inhibitors have shown little clinical efficacy. We look forward to continuing our efforts to advance this important program toward clinical-stage," commented Dr. Bissonnette.
For the preclinical study, mice were implanted with either CT26 or Colon26 cells, both mouse models of MSS/MMRp CRC. The mice were treated with anti-CTLA-4 and either daily or biweekly DNase I (administered either ip or iv). Response was monitored by measuring tumor volume.
Key Highlights
Data demonstrates beneficial effects of targeting NETs with systemic DNase I in models of primary tumor and metastatic CRC, improving the efficacy of CTLA-4 immune checkpoint blockade.
Both published and newer data suggests that DNase I impedes neutrophil tumor infiltration, promotes CD4 and CD8 T cell infiltration, and enhances intratumoral T cell activation.
DNase I plus 𝛼-CTLA-4 combination therapy results in tumor growth inhibition, several CRs and enhanced survival in mice bearing CT26 or Colon26 MSS/MMRp CRC tumors.
Dose response evaluations of DNase I combined with 𝛼-CTLA-4, examining both route and frequency of administration was performed.
DNase I plus 𝛼-CTLA-4 combination therapy resulted in complete responses (CRs) in mice bearing either CT26 or Colon26 tumors.
Significantly, rechallenge of Colon26 and CT26 complete responder animals resulted in no (0 mm3) tumor take or growth, suggesting that DNase I combined with 𝛼-CTLA-4 promoted antitumor immunity and immunological memory.
Xenetic's DNase-based oncology platform is designed to target NETs, which are weblike structures composed of extracellular chromatin coated with histones and other proteins. In cancer, NETs are expelled by activated neutrophils into the TME and blood, thereby promoting cancer spread and local and systemic immunosuppression. Reduction of NETs burden via application of Xenetic's proprietary recombinant human DNase I has been shown to improve efficacy of immunotherapy, adoptive cell therapy and chemotherapy in preclinical animal models.
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 locally advanced or metastatic solid tumors.
For more information, please visit the Company's website at www.xeneticbio.com and connect on X , 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", "making", and other words of similar meaning, including, but not limited to: all statements regarding our DNase-based oncology platform, including statements regarding: focusing on advancing innovative immuno-oncology technologies addressing hard to treat oncology indications; continued encouragement by the data demonstrated by our DNase platform technology; continued our efforts to advance this important program toward clinical-stage; ; 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 into the clinic as an adjunctive therapy for pancreatic carcinoma and locally advanced or metastatic solid tumors. All 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 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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