Altamira Therapeutics Announces Significant Enhancement of Immune Checkpoint Inhibition Therapy in Combination with Zbtb46 mRNA Delivered with SemaPhore Nanoparticles in Animal Tumor Models
Altamira Therapeutics announced significant enhancement of immune checkpoint inhibition therapy using Zbtb46 mRNA delivered with SemaPhore Nanoparticles in animal tumor models. Key findings published in Nature Immunology include:
1. Zbtb46 mRNA nanoparticles significantly reduced tumor growth (p<0.0001).
2. Combination with anti-PD1 showed synergistic control of tumor growth and long-term complete remission in many cases.
3. Treatment may help more solid tumor patients respond to anti-PD1 therapies.
4. Zbtb46 expression boosted tumor vessel normalization and enhanced antitumor immunity.
5. Results highlight potential of SemaPhore platform for delivering mRNA therapeutics to non-hepatic tissues.
Altamira Therapeutics ha annunciato un significativo miglioramento della terapia con inibizione dei checkpoint immunitari utilizzando mRNA Zbtb46 somministrato con Nanoparticelle SemaPhore in modelli animali di tumore. I principali risultati pubblicati in Nature Immunology includono:
1. Le nanoparticelle di mRNA Zbtb46 hanno ridotto significativamente la crescita del tumore (p<0.0001).
2. La combinazione con anti-PD1 ha mostrato un controllo sinergico della crescita tumorale e una remissione completa a lungo termine in molti casi.
3. Il trattamento potrebbe aiutare più pazienti con tumori solidi a rispondere alle terapie anti-PD1.
4. L'espressione di Zbtb46 ha migliorato la normalizzazione dei vasi tumorali e potenziato l'immunità antitumorale.
5. I risultati evidenziano il potenziale della piattaforma SemaPhore per la somministrazione di terapie mRNA ai tessuti non epatici.
Altamira Therapeutics anunció una mejora significativa en la terapia de inhibición de puntos de control inmunitarios utilizando mRNA Zbtb46 administrado con NanoPartículas SemaPhore en modelos de tumor en animales. Los hallazgos clave publicados en Nature Immunology incluyen:
1. Las nanopartículas de mRNA Zbtb46 redujeron significativamente el crecimiento del tumor (p<0.0001).
2. La combinación con anti-PD1 mostró un control sinérgico del crecimiento tumoral y remisión completa a largo plazo en muchos casos.
3. El tratamiento podría ayudar a más pacientes con tumores sólidos a responder a las terapias anti-PD1.
4. La expresión de Zbtb46 potenciaba la normalización de los vasos tumorales y mejoraba la inmunidad antitumoral.
5. Los resultados resaltan el potencial de la plataforma SemaPhore para entregar terapias de mRNA a tejidos no hepáticos.
알타미라 테라퓨틱스(Altamira Therapeutics)는 동물 종양 모델에서 SemaPhore 나노입자와 함께 전달된 Zbtb46 mRNA를 사용하여 면역 체크포인트 억제 요법의 중요한 향상을 발표했습니다. Nature Immunology에 발표된 주요 발견은 다음과 같습니다:
1. Zbtb46 mRNA 나노입자가 종양 성장률을 의미 있게 감소시켰습니다 (p<0.0001).
2. 항-PD1과의 조합은 종양 성장에 대한 시너지 효과를 보였으며 많은 사례에서 장기적인 완전 관해를 나타냈습니다.
3. 이 치료법은 더 많은 고형 종양 환자가 항-PD1 치료에 반응할 수 있도록 도울 수 있습니다.
4. Zbtb46의 발현이 종양 혈관의 정상화를 촉진하고 항종양 면역을 강화했습니다.
5. 결과는 SemaPhore 플랫폼이 비간 조직에 mRNA 치료제를 전달하는 잠재력을 강조합니다.
Altamira Therapeutics a annoncé une amélioration significative de la thérapie d'inhibition des points de contrôle immunitaires en utilisant l'ARNm Zbtb46 livré avec des nanoparticules SemaPhore dans des modèles de tumeurs animales. Les principales conclusions publiées dans Nature Immunology incluent :
1. Les nanoparticules d'ARNm Zbtb46 ont significativement réduit la croissance tumorale (p<0.0001).
2. La combinaison avec un anti-PD1 a montré un contrôle synergique de la croissance tumorale et une rémission complète à long terme dans de nombreux cas.
3. Le traitement pourrait aider plus de patients ayant des tumeurs solides à répondre aux thérapies anti-PD1.
4. L'expression de Zbtb46 a favorisé la normalisation des vaisseaux tumoraux et amélioré l'immunité antitumorale.
5. Les résultats soulignent le potentiel de la plateforme SemaPhore pour la livraison de thérapies à base d'ARNm aux tissus non hépatiques.
Altamira Therapeutics gab eine erhebliche Verbesserung der Immun-Checkpoint-Inhibitionstherapie durch den Einsatz von Zbtb46 mRNA, die mit SemaPhore-Nanopartikeln in Tiertumormodellen verabreicht wurde, bekannt. Wichtige Ergebnisse, die in Nature Immunology veröffentlicht wurden, umfassen:
1. Zbtb46-mRNA-Nanopartikel reduzierten das Tumorwachstum signifikant (p<0.0001).
2. Die Kombination mit anti-PD1 zeigte eine synergistische Kontrolle des Tumorwachstums und bei vielen Fällen eine langfristige vollständige Remission.
3. Die Behandlung könnte mehr Patienten mit soliden Tumoren helfen, auf anti-PD1-Therapien zu reagieren.
4. Die Expression von Zbtb46 förderte die Normalisierung der Tumorgefäße und verbesserte die antitumorale Immunität.
5. Die Ergebnisse heben das Potenzial der SemaPhore-Plattform zur Verabreichung von mRNA-Therapeutika an nicht-hepatische Gewebe hervor.
- Significant reduction in tumor growth with Zbtb46 mRNA nanoparticles (p<0.0001)
- Synergistic effect when combined with anti-PD1 therapy, leading to long-term complete remission in many cases
- Potential to expand the efficacy of immune checkpoint inhibitors to a larger cancer patient population
- Publication of results in Nature Immunology, a top-tier scientific journal
- Demonstration of SemaPhore platform's potential for non-hepatic mRNA therapeutics delivery
- None.
Insights
The publication in Nature Immunology showcases a significant breakthrough in cancer treatment. The study demonstrates that Zbtb46 mRNA delivered via SemaPhore nanoparticles can substantially reduce tumor growth (
This approach could potentially expand the efficacy of immune checkpoint inhibitors to a broader patient population, addressing a critical limitation in current cancer immunotherapy. The ability to normalize tumor vasculature and enhance anti-tumor immunity through Zbtb46 expression is a novel mechanism that could revolutionize solid tumor treatment strategies.
The development of protective immunological memory in treated mice is particularly exciting, suggesting potential for long-term cancer prevention. This research opens new avenues for combination therapies in oncology, potentially improving outcomes for patients with previously treatment-resistant tumors.
Altamira Therapeutics' SemaPhore technology demonstrates significant potential in the rapidly growing field of mRNA therapeutics. The successful delivery of Zbtb46 mRNA to non-hepatic tissues addresses a key challenge in the industry, potentially expanding the application of mRNA beyond vaccines into cancer treatment.
This breakthrough could position Altamira as a key player in the next generation of cancer immunotherapies. The synergistic effect with existing checkpoint inhibitors like Keytruda and Opdivo suggests potential for lucrative partnerships or licensing agreements with major pharmaceutical companies.
Investors should note that while these results are promising, they are still at the preclinical stage. The path to clinical trials and eventual commercialization will require substantial time and capital investment. However, the publication in a prestigious journal like Nature Immunology lends credibility to the technology and may attract attention from both the scientific community and potential investors or partners.
Hamilton, Bermuda, Aug. 12, 2024 (GLOBE NEWSWIRE) --
- Treatment with ZbtbB46 mRNA nanoparticles based on Altamira’s SemaPhore™ delivery technology results in significant reduction in tumor growth (p<0.0001)
- Combination of nanoparticles with immune checkpoint inhibitor (anti-PD1) shows even more pronounced improvement, synergistic control of tumor growth with long-term complete remission of tumor in many cases
- Combination therapy may help to render more solid tumor patients responsive to anti-PD1 therapies (immune checkpoint inhibitors)
- Results published in Nature Immunology, one of the world’s top immunology journals
Altamira Therapeutics Ltd. (“Altamira” or the “Company”) (Nasdaq:CYTO), a company dedicated to developing and commercializing RNA delivery technology for targets beyond the liver, today announced the publication of a peer-reviewed article in Nature Immunology highlighting the important role of the Zbtb46 gene in the control of tumor growth and demonstrating a significant reduction in tumor growth in vivo through treatment with Zbtb46 mRNA delivered with Altamira’s SemaPhore™ nanoparticle technology.1 The treatment effect was potentiated when combined with anti-PD1 immune checkpoint inhibition, inducing long-term remission and promoting immunological memory. The research was conducted by a group around Professor Kyunghee Choi of the Pathology & Immunology Department of Washington University School of Medicine (St. Louis, MO).
“Immune checkpoint inhibitors such as Keytruda2 or Opdivo3 have shown remarkable efficacy in treating a broad range of solid tumors, but unfortunately a large number of patients are unable to benefit from them due to an immunosuppressive tumor microenvironment”, observed Samuel Wickline, M.D., Altamira’s Chief Scientific Adviser and a co-author of the publication. “The study from the Choi Lab shows impressive results from boosting Zbtb46 expression with tumor vessel normalization and enhanced antitumor immunity. Administration of Zbtb46 mRNA nanoparticles appears to provide the right conditions for anti-PD1 treatments to work in a substantially larger cancer population, helping to control tumor growth, induce long-term remission and promote immunological memory. The exciting results with Zbtb46 mRNA nanoparticles are just another great example highlighting the potential of the SemaPhore platform for delivering mRNA therapeutics to non-hepatic tissues.”
The research group studied the role of the Zbtb46 (Zinc finger and BTB domain-containing protein 46) gene in the progression of solid tumors and in tumor angiogenesis and anti-tumor immunity. Cancers require the formation of new blood vessels (tumor angiogenesis) to grow and metastasize, supplying their cells with a supportive microenvironment rich with oxygen and nutrients. In addition, the newly formed vasculature within the tumor microenvironment may block the infiltration of T cells, thus suppressing an appropriate immune response and preventing the killing of cancer cells. The researchers found that downregulation of Zbtb46 resulted in a pro-tumor microenvironment, including dysfunctional vasculature and immunosuppressive cell accumulation. In contrast, enforced Zbtb46 expression mitigated the pro-tumor microenvironment features and restricted tumor growth. These findings suggest that ZBTB46 is a critical factor for angiogenesis and immunosuppressive conditions in the tumor microenvironment and could be a promising target for cancer treatment.
In a next step, the group tested the systemic delivery of Zbtb46 mRNA with SemaPhore nanoparticles in mouse models of sarcoma and metastatic breast cancer to boost Zbtb46 expression. The treatment resulted in sustained Zbtb46 expression, a restored immunostimulatory tumor microenvironment and a highly significant reduction in tumor growth (p<0.0001). Further, the Zbtb46 mRNA nanoparticle treatment was combined with an immune checkpoint inhibitor (anti-PD1) treatment, which resulted in even better outcomes. The authors reported: “Remarkably, Zbtb46 nanoparticles induced dramatic anti-PD1 response in both anti-PD1-responsive [sarcoma] and anti-PD1-refractory [breast cancer] tumor models, generating long-term complete remission of tumor in many of the treated animals.” Extended monotherapy with Zbtb46 nanoparticles produced complete remission even in mice refractory to anti-PD1 treatment. Addition of a VEGF inhibitor to the combination therapy further enhanced the treatment response. Mice whose sarcoma was eliminated through treatment did not develop fresh cancers following repeated challenge, indicating the development of a protective immunological memory.
About SemaPhore
SemaPhore is a versatile platform designed to enable safe and effective delivery of mRNA into target cells, using systemic or local administration. It is based on a proprietary 21 amino acid peptide that can engage any type of RNA in rapid self-assembly into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach target tissues other than the liver. SemaPhore protects the RNA payload from degradation in the circulation and allows for rapid and effective cell entrance. Efficient delivery and positive treatment outcomes have been demonstrated in multiple murine models of disease so far.
About Altamira Therapeutics
Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a
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1 Kabir AU et al. (2024), ZBTB46 coordinates angiogenesis and immunity to control tumor outcome, Nat Immunol https://www.nature.com/articles/s41590-024-01936-4.
2 Keytruda (pembrolizumab) is a trademark of Merck Sharp & Dohme Corp.
3 Opdivo (nivolumab) is a trademark of the Bristol-Myers Squibb Company.
FAQ
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