MI-O-101

  • Based on a non-infectious Cowpea mosaic virus (CPMV) nanotechnology platform. 

  • Robust anti-tumor responses in preclinical studies across multiple tumor types.

  • Human immune cell activation is consistent with immune activation in pre-clinical animal models.

  • Potential in veterinary medicine supported by positive data in dogs with spontaneous cancer. 

  • Pre-clinical study results support combination potential with current standard of care including chemotherapy, radiation and checkpoint inhibitors. 

MI-O-101

Checkpoint inhibitors as a stand-alone therapy can provide significant life changing benefit for many cancer patients, however the majority of patients have incomplete or even no response to therapy.  Why and how patients respond to checkpoint inhibitors appears to be determined by the immunological status of the environment within their cancer.  Scientists and clinicians in immunotherapy describe tumors as either immunologically “cold” meaning the immune system in the tumor is suppressed or they are immunologically “hot” indicating that the local tumor immune response is more active and thus can respond more readily to checkpoint inhibitor treatment.  


Mosaic IE’s MI-O-101 program is based on a CPMV based nanoparticle that was carefully selected because of its features that allow it to stimulate a particularly strong immune response when delivered into the tumor. Despite the fact that the nanoparticle is non-infectious, the immune cells inside the tumor immediately sees it as a foreign pathogen because of its structural characteristics and genetic material.  The approximately one trillion nanoparticles delivered with each injection cause the innate immune cells to immediately signal the local immune system into action by through immune signaling resulting in what is effectively a call to arms. The activated immune response inside the tumor results in an attack on the nanoparticle however this also results in the destruction of tumor cells leading to the release of tumor antigens that trigger a further anti-tumor immune response.    


More specifically, MI-O-101 converts a “cold” tumor into a “hot” tumor via an intra-tumoral cytokine and chemokine response through activation of Toll- Like Receptors on the resident innate immune cells, inducing activation of tumor-associated macrophages and neutrophils with recruitment of dendritic cells and natural killer cells.  In addition, it converts pre-existing immunosuppressive myeloid cells into activated antigen-presenting cells, improving effector and memory T cell responses thereby creating systemic tumor-specific cytotoxic CD8+ T cell activity.  The result is conversion of an immunosuppressive tumor microenvironment into an anti-tumor microenvironment with a systemic search and destroy function that attacks not only the local tumor but also other tumor sites through immune surveillance which is referred to as an “abscopal effect”.


In preclinical studies, MI-O-101 has been combined with other current standard of care treatments including chemotherapy, radiation and checkpoint inhibitors to further boost the effect of treatment.  The experiments have validated the potential of combination therapy that can result in complete destruction of the primary tumor, destruction of other tumors via the abscopal effect and even protection against re-challenge with the same tumor type. We expect to advance MI-O-101 into human clinical studies in 2021.  

Unleashing the Power of the Immune System

The immune system carries the potential to destroy undetected metastases

The CPMV intratumoral immunotherapy is used to activate the immune system and launch the cancer immunity cycle:

  • While non-infectious towards mammals, CPMV is highly visible to the immune system.

  • CPMV nanoparticles have highly organized and repetitive structures that activate the innate immune system through pattern recognition receptors.

  • Once MI-O-101 is delivered into an identified tumor, MI-O-101 activates the innate immune system and remodels the tumor microenvironment.

Cancer Immunity Cycle

Recruited and activated innate immune cells induce cancer cell killing, tumor antigen processing, ultimately launching systemic anti-tumor immunity.

Intratumoral immunotherapy reverses the immunosuppressive phenotype and primes systemic anti-tumor immunity, eliminating the treated tumor and metastatic disease.  These immune-stimulatory properties in combination with their size, make the CPMV nanoparticles ideal candidates for vaccine delivery to the draining lymph nodes and priming interactions with antigen-presenting cells (APCs).

MI-O-101 vs. Traditional Cancer Immunotherapy

  • MI-O-101 introduced directly into the tumor microenvironment after tumors are established elicits a potent anti-tumor response.

  • MI-O-101 is not cytolytic to tumor cells; effects are immune-mediated.

  • MI-O-101 treatment activates neutrophils (tumor killing function, cytokine secretion) and cytotoxic and memory T cells (adaptive).

  • MI-O-101 downregulates MDSCs and expands tumor-specific T- cells (as indicated by upregulation of MHC II and CD86) – and therefore is distinct from checkpoint inhibitors that are not tumor-specific.

MI-O-101 immune activation steps:

  • Upon administration into the tumor, MI-O-101 is seen as a foreign invader even though it is non-infectious.  MI-O-101 was specifically selected to elicit a strong immune response.

  • The local innate immune system activates. The main purpose of the innate immune response is to immediately prevent the spread and movement of foreign pathogens throughout the body.  The MI-O-101 intratumoral injection contains approximately a trillion nanoparticles that are seen and recognized as "foreign pathogens".  

  • The activated innate immune system responds immediately by working through a cascade of events in order to remove the "foreign invaders" through the army of immune cells that activate to fight the pathogens.

  • Part of this response is to shut down local immune suppression that normally protects the body from an overactive immune response however in the case of a tumor the immune suppression is enhanced by the tumor.

  • Chemical messengers, known as cytokines, are released that further the attack on the "foreign invader".  During the attack, nearby tumor cells are destroyed resulting in targets, known as tumor antigens, being released which are subsequently recognized by the adaptive immune system.

  • The innate and adaptive immune responses are boosted through the periodic introduction of MI-O-101 which eventually results in an adaptive immune response that is long-lasting. 

  • In addition, the activated innate immune response spreads beyond the injected tumor throughout the body as part of immune surveillance, resulting in the recognition of metastatic disease and foreign tumor sites. 

  • Eventually, the immune response can result in a long term immune response that has the potential to fight existing cancer as well as future recurrence.

© 2020 by Mosaic ImmunoEngineering Inc.