Our Science

How Neospora Locates, Infiltrates, and Destroys Solid Cancers - Overview

How Neospora therapy eliminates tumors.

  1. Neospora introduced either locally (peri- or intra-tumorally), or at distance (subcutaneously), biodistributes rapidly throughout the system.

  2. Neospora localizes and rapidly penetrates the TME that it colonizes, but it does not harm normal tissues where it is rapidly neutralized. The net effect is concentration and infection of tumors in the body.

  3. Obligate intracellular organisms, Neospora enter tumor cells and replicate, causing lysis with release of replicants and neoantigens.

  4. In addition, Neospora engineered with transgenes synthesizes the encoded molecules for either expression on surface, or secreted into the tumor environment.

A Quick Profile of Neospora, a paradigm-shifting, multifunctional anti-tumor platform based on oncolytic eukaryotic microbes or protozoa.

Neospora is very different from previous generation oncolytic microbes; it is much larger and multifunctional. It is also among the most genetically stable of organisms, and is not pathogenic to humans or to normal human tissues.

  1. Neospora caninum is an obligate intracellular micro-organism that is a eukaryote, a high order life form with a nucleated cell with a genetic mass of some 62 Mb i.e. about 1,500 times more than an Adenovirus'

  2. It is a member of the Phylum Apicomplexa, protozoa that have evolved with organelles and mechanisms to penetrate and infiltrate almost any mammalian cell, characterized by the Apical Complex.

  3. Neospora has a complex, multiphasic life cycle, only one of which, the tachyzoite, is actively motile, infective and replicative.

  4. The dog is the normal definitive host, and farm animals are intermediate hosts. However, Neospora is considered not pathogenic to humans, and can be handled with the lowest level of Biosafety, BSL1.

Schematic view of Neospora in tachyzoite form

Neospora caninum is from the Phylum Apicomplexa, which consist of efficient intracellular infective agents that evolved organelles and mechanisms to enter across almost any mammalian cell membrane. Only the tachyzoite form is motile, infiltrative, and replicative.

Comparison of Viral Vectors to Neospora

  • Neospora is a eukaryote, a nucleated cell, with organelles as in animal cells. It replicates, and synthesizes protein "in-house".

  • It does not involve either the host cancer cell genome or its machinery; there is no transduction of genetic material.

  • Orders of magnitude larger and more complex than viruses and becteria, the maximum payload for Neospora has not been determined.

Neospora caninum is very genetically stable, and would not involve the genome of host cancer cells.

(See Figure 1) As a eukaryote with a genome approaching 62 Mb, Neospora is an organism that is expected to spontaneously mutate by 1% in 50-100 million years. In foreseeable human future, Neospora would not spontaneously mutate.

In contrast, a small virus frequently mutates, with 1% spontaneous mutation every 1 month to 1 year, and, as it requires the use of the host cell's reproductive machinery with transduction of viral genes, there is potential for mutagenic effect on a cancer's genome.

Tumor Penetration and Infiltration is an evolutionary invasion design of Apicomplexae protozoa.

An Apicomplexa tachyzoite traverses a collagen matrix representing the ECM in a tumor.

A helical twisting motility is observed as the tachyzoite (motile) phase form weaves through collagen fibers. Source: "Coupling Polar Adhesion with Traction, Spring, and Torque Forces Allows High-Speed Helical Migration of the Protozoan Parasite Toxoplasma" Georgios Pavlou, Bastien Touquet, Luis Vigetti, Patricia Renesto, Alexandre Bougdour, Delphine Debarre, Martial Balland, and Isabelle Tardieux ACS Nano 2020 14 (6), 7121-7139 DOI: 10.1021/acsnano.0c01893

Apicomplexa attaches to and penetrates most mammalian cells.

Apicomplexa like Neospora have evolved an efficient motile penetrating property that is unimpeded by the tumor matrix, and can enter almost any mammalian cell. First contact is its narrow "Apical Complex" that glides on host cells' surface before adhering, opening a membrane "doorway", and then propelling itself into the host cell.