Altamira Therapeutics’ SemaPhore Delivery Platform Shows Significant Synergis-tic Effects of ZBTB46 mRNA with PD1 Immunotherapy in Control of Tumor Growth in Animal Model


  • Preprint of results from animal study shows restriction of tumor growth in mice treated with ZBTB46 mRNA nanoparticles based on Altamira’s SemaPhore™ delivery technology
  • Nanoparticle treatment combined with immune checkpoint inhibitor results in synergistic control of tumor growth

Altamira Therapeutics ("Altamira" or the "Company") (Nasdaq:CYTO), a company dedicated to developing RNA-based therapeutics that address important unmet medical needs, today announced the release of animal data by a Washington University School of Medicine (St. Louis, MO) research group showing restriction of tumor growth with a novel mRNA therapeutic delivered in nanoparticles based on the Company’s SemaPhore™ delivery platform.

Expression of the ZBTB46 gene with SemaPhore was associated with an immunostimulatory tumor microenvironment (TME), and it was potentiated when combined with anti-PD1 immune checkpoint inhibition. The manuscript describing the study is available on a preprint server1 and has been submitted to a scientific journal for peer-review and potential publication.

The research group, led by Professor Kyunghee Choi of the Pathology & Immunology Department of Washington University, was interested in understanding the role that the ZBTB46 (Zinc Finger and BTB Domain Containing 46) gene plays in the microenvironment of tumors. The researchers found that tumor-derived factors frequently downregulate ZBTB46 resulting in a pro-tumor microenvironment, characterized by dysfunctional vasculature and immunosuppressive cell accumulation. In contrast, enforced ZBTB46 expression mitigated the pro-tumor TME features and restricted tumor growth, suggesting ZBTB46 as a potential target for tumor treatment.

In a next step, the group tested the systemic delivery of ZBTB46 mRNA with Altamira’s peptide-based SemaPhore nanoparticles in mouse models of sarcoma and metastatic breast cancer to boost ZBTB46 expression. The treatment sustained ZBTB46 expression in tumor-dendritic cells and -endothelial cells and resulted in the restriction of tumor growth associated with an immunostimulatory TME.

When combining nanoparticle treatment with an immune checkpoint inhibitor, the researchers reported that, “remarkably, the nanoparticles induced dramatic response in both anti-PD1-responsive […] and -refractory [..] tumor models following the treatment, generating long-term complete remission of tumor mass in many of the treated animals challenged with the anti-PD1-responsive [..] tumor.” They concluded that enforcing ZBTB46 expression promoted anti-tumor components in the TME, a prerequisite for effective immune checkpoint blockade therapy, and could be an effective adjuvant therapy with immunotherapy in cancer management.  

Samuel Wickline, M.D., Altamira’s Chief Scientific Adviser and a co-author of the manuscript, commented: “The tumor microenvironment is known to play a key role in cancer growth. This latest study from the Choi Lab not only identified ZBTB46 as a key element in the interaction between tumor growth and tumor microenvironment, but also demonstrated how boosting its expression by using mRNA can help to attenuate tumor growth. In addition, it showed very promising synergistic effects with a well-known immune checkpoint inhibitor. Our SemaPhore nanoparticles have been designed to reach target diseased cells with systemic administration and efficiently deliver mRNA therapeutics inside those cells, and we believe that there is significant potential for them supporting the development of novel cancer treatment options.”

About SemaPhore

SemaPhore is a versatile platform designed to allow for safe and effective delivery of mRNA (messenger ribonucleic acid) into target cells. It is based on a patented 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 other target tissues than the liver. SemaPhore protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide endosomal escape and cytoplasmic delivery. Effective delivery of mRNA and positive treatment outcomes have been demonstrated in various murine models of disease, including osteoarthritis (WNT16), atherosclerosis (p27Kip1) and aortic aneurysm (SOD2).

About Altamira Therapeutics

Altamira Therapeutics (Nasdaq:CYTO) is dedicated to developing RNA-based therapeutics for extrahepatic targets (OligoPhore™ / SemaPhore™ delivery platforms). The Company currently has two flagship siRNA programs in preclinical development beyond in vivo proof of concept: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis. The versatile delivery platform is also suited for mRNA and other types of RNA therapeutics and shall be leveraged via out-licensing to pharma or biotech companies. In addition, Altamira is in the process of divesting and/or licensing-out its legacy assets in allergology and viral infection (Bentrio® OTC nasal spray; commercial) and inner ear therapeutics (AM-125 nasal spray for vertigo; post Phase 2; Keyzilen® and Sonsuvi® for tinnitus and hearing loss; Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit:

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